Search "ماده 96 قانون مالیات" (2024)

CloseAgents responsible for reactive airways dysfunction syndromeAgents responsible for reactive airways dysfunction syndrome Agent Type of investigation Evidence Reference Acetic acid Epidemiological H, S, BHR Am Rev Respir Dis 1991; 144:1058 Case report H, S, P Br J Ind Med 1989; 46:67 Chloridic acid Case report H, S, BHRChest 1988; 94:476 Chest 1990; 98:928 Sulfuric acid Case report H, S, BHR Chest 1988; 94:476 Various acids Case report H, S, BHR, P Chest 1994; 105:1895 Case report H, S, BHR Chest 1989; 96:297 Bleaching agent Case report H, S, BHR Chest 1988; 94:476 Cleaning agents Case report H, S Chest 1976; 69:372 Sealing agents Case report H, S, BHR Chest 1985; 88:376 Ammonia Case report H, S Mayo Clin Proc 1983; 58:389 Case report H, S, P Thorax 1992; 47:755 Phtalic anhydride Case report H, S, BHR Rev Pneumol Clin 1993; 49:247 Bromochlorodifluoromethane (Halon 1211) Case report H, S, BHR Occup Env Med 2004; 61:712 Bromotrifluoromethane (Halon 1301) Case report H, S Eur Respir J 1999; 13:1192 Chlorine Epidemiological H, S, BHR Occup Env Med 1994; 51:225 Clinical study H, S, BHR, PJ Allergy Clin Immunol 1994; 93:12 Eur Respir J 1997; 10:241 Chlorofluorocarbons (CFC) Clinical study H, S, BHR, P Scand J Work Environ Health 2003; 29:71 Chloropicrin Experimental P Toxicol Appl Pharm 1984; 74:417 Metal coat remover Case report H, S, BHR Chest 1985; 88:376 Diesel Case report H, S, BHR J Occup Med 1993; 35:149 Diethylaminoethanol Epidemiological H, S J Occup Med 1994; 36:623 Sulfur dioxide Case report H, S, BHR, PChest 1990; 98:928 Am Rev Respir Dis 1979; 119:555 Case report H, S, BHR Chest 1989; 96:297 Epichlorohydrin Experimental P Toxicol Appl Pharm 1984; 74:417 Fire/smoke Case report H, S, BHR Chest 1988; 94:476 Case report H, S J Occup Med 1991; 33:458 Formalin Case report H, S Lancet 1975; 2:603 Formaldehyde Case report H, S, BHR Allergy 2004; 59:115 Hydrazin Case report H, S, BHR Chest 1985; 88:376 Iodine Case report H, S, BHR, P Ind Health 2009; 47:681 Diisocyanates Case report H, S, BHR Scand J Work Environ Health 1981; 7:310 Case report H, S, BHR, P Allergy 1996; 51:262 Experimental S Toxicol App Pharmacol 1987; 89:332 Case report H, S, BHR Chest 1989; 96:297 Calcium oxide Case report H, S, BHR Chest 1989; 96:297 Ethylene oxide Case report H, S, BHR, P Br J Ind Med 1992; 49:523 Heated paints Case report H, S, BHR Chest 1989; 96:297 Pulverized paints Case report H, S, BHR, PChest 1989; 96:297 Chest 1985; 88:376 Perchloroethylene Case report H, S, BHR Chest 1988; 94:476 Vapors (chlorine, mustard, phosgene, etc) Case report H, P Br Med J 1915; 165H: history; S: spirometry; BHR: bronchial hyperresponsiveness; P: pathology.Graphic 55545 Version 5.0

CloseBlood pressure levels for males by age and height percentileBlood pressure levels for males by age and height percentile BP (percentile) Systolic BP (mmHg) Diastolic BP (mmHg) Height percentile or measured height Height percentile or measured height 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95% 1 year Height (in) 30.4 30.8 31.6 32.4 33.3 34.1 34.6 30.4 30.8 31.6 32.4 33.3 34.1 34.6 Height (cm) 77.2 78.3 80.2 82.4 84.6 86.7 87.9 77.2 78.3 80.2 82.4 84.6 86.7 87.9 50th 85 85 86 86 87 88 88 40 40 40 41 41 42 42 90th 98 99 99 100 100 101 101 52 52 53 53 54 54 54 95th 102 102 103 103 104 105 105 54 54 55 55 56 57 57 95th + 12 mmHg 114 114 115 115 116 117 117 66 66 67 67 68 69 69 2 years Height (in) 33.9 34.4 35.3 36.3 37.3 38.2 38.8 33.9 34.4 35.3 36.3 37.3 38.2 38.8 Height (cm) 86.1 87.4 89.6 92.1 94.7 97.1 98.5 86.1 87.4 89.6 92.1 94.7 97.1 98.5 50th 87 87 88 89 89 90 91 43 43 44 44 45 46 46 90th 100 100 101 102 103 103 104 55 55 56 56 57 58 58 95th 104 105 105 106 107 107 108 57 58 58 59 60 61 61 95th + 12 mmHg 116 117 117 118 119 119 120 69 70 70 71 72 73 73 3 years Height (in) 36.4 37.0 37.9 39.0 40.1 41.1 41.7 36.4 37.0 37.9 39.0 40.1 41.1 41.7 Height (cm) 92.5 93.9 96.3 99.0 101.8 104.3 105.8 92.5 93.9 96.3 99.0 101.8 104.3 105.8 50th 88 89 89 90 91 92 92 45 46 46 47 48 49 49 90th 101 102 102 103 104 105 105 58 58 59 59 60 61 61 95th 106 106 107 107 108 109 109 60 61 61 62 63 64 64 95th + 12 mmHg 118 118 119 119 120 121 121 72 73 73 74 75 76 76 4 years Height (in) 38.8 39.4 40.5 41.7 42.9 43.9 44.5 38.8 39.4 40.5 41.7 42.9 43.9 44.5 Height (cm) 98.5 100.2 102.9 105.9 108.9 111.5 113.2 98.5 100.2 102.9 105.9 108.9 111.5 113.2 50th 90 90 91 92 93 94 94 48 49 49 50 51 52 52 90th 102 103 104 105 105 106 107 60 61 62 62 63 64 64 95th 107 107 108 108 109 110 110 63 64 65 66 67 67 68 95th + 12 mmHg 119 119 120 120 121 122 122 75 76 77 78 79 79 80 5 years Height (in) 41.1 41.8 43.0 44.3 45.5 46.7 47.4 41.1 41.8 43.0 44.3 45.5 46.7 47.4 Height (cm) 104.4 106.2 109.1 112.4 115.7 118.6 120.3 104.4 106.2 109.1 112.4 115.7 118.6 120.3 50th 91 92 93 94 95 96 96 51 51 52 53 54 55 55 90th 103 104 105 106 107 108 108 63 64 65 65 66 67 67 95th 107 108 109 109 110 111 112 66 67 68 69 70 70 71 95th + 12 mmHg 119 120 121 121 122 123 124 78 79 80 81 82 82 83 6 years Height (in) 43.4 44.2 45.4 46.8 48.2 49.4 50.2 43.4 44.2 45.4 46.8 48.2 49.4 50.2 Height (cm) 110.3 112.2 115.3 118.9 122.4 125.6 127.5 110.3 112.2 115.3 118.9 122.4 125.6 127.5 50th 93 93 94 95 96 97 98 54 54 55 56 57 57 58 90th 105 105 106 107 109 110 110 66 66 67 68 68 69 69 95th 108 109 110 111 112 113 114 69 70 70 71 72 72 73 95th + 12 mmHg 120 121 122 123 124 125 126 81 82 82 83 84 84 85 7 years Height (in) 45.7 46.5 47.8 49.3 50.8 52.1 52.9 45.7 46.5 47.8 49.3 50.8 52.1 52.9 Height (cm) 116.1 118.0 121.4 125.1 128.9 132.4 134.5 116.1 118.0 121.4 125.1 128.9 132.4 134.5 50th 94 94 95 97 98 98 99 56 56 57 58 58 59 59 90th 106 107 108 109 110 111 111 68 68 69 70 70 71 71 95th 110 110 111 112 114 115 116 71 71 72 73 73 74 74 95th + 12 mmHg 122 122 123 124 126 127 128 83 83 84 85 85 86 86 8 years Height (in) 47.8 48.6 50.0 51.6 53.2 54.6 55.5 47.8 48.6 50.0 51.6 53.2 54.6 55.5 Height (cm) 121.4 123.5 127.0 131.0 135.1 138.8 141.0 121.4 123.5 127.0 131.0 135.1 138.8 141.0 50th 95 96 97 98 99 99 100 57 57 58 59 59 60 60 90th 107 108 109 110 111 112 112 69 70 70 71 72 72 73 95th 111 112 112 114 115 116 117 72 73 73 74 75 75 75 95th + 12 mmHg 123 124 124 126 127 128 129 84 85 85 86 87 87 87 9 years Height (in) 49.6 50.5 52.0 53.7 55.4 56.9 57.9 49.6 50.5 52.0 53.7 55.4 56.9 57.9 Height (cm) 126.0 128.3 132.1 136.3 140.7 144.7 147.1 126.0 128.3 132.1 136.3 140.7 144.7 147.1 50th 96 97 98 99 100 101 101 57 58 59 60 61 62 62 90th 107 108 109 110 112 113 114 70 71 72 73 74 74 74 95th 112 112 113 115 116 118 119 74 74 75 76 76 77 77 95th + 12 mmHg 124 124 125 127 128 130 131 86 86 87 88 88 89 89 10 years Height (in) 51.3 52.2 53.8 55.6 57.4 59.1 60.1 51.3 52.2 53.8 55.6 57.4 59.1 60.1 Height (cm) 130.2 132.7 136.7 141.3 145.9 150.1 152.7 130.2 132.7 136.7 141.3 145.9 150.1 152.7 50th 97 98 99 100 101 102 103 59 60 61 62 63 63 64 90th 108 109 111 112 113 115 116 72 73 74 74 75 75 76 95th 112 113 114 116 118 120 121 76 76 77 77 78 78 78 95th + 12 mmHg 124 125 126 128 130 132 133 88 88 89 89 90 90 90 11 years Height (in) 53.0 54.0 55.7 57.6 59.6 61.3 62.4 53.0 54.0 55.7 57.6 59.6 61.3 62.4 Height (cm) 134.7 137.3 141.5 146.4 151.3 155.8 158.6 134.7 137.3 141.5 146.4 151.3 155.8 158.6 50th 99 99 101 102 103 104 106 61 61 62 63 63 63 63 90th 110 111 112 114 116 117 118 74 74 75 75 75 76 76 95th 114 114 116 118 120 123 124 77 78 78 78 78 78 78 95th + 12 mmHg 126 126 128 130 132 135 136 89 90 90 90 90 90 90 12 years Height (in) 55.2 56.3 58.1 60.1 62.2 64.0 65.2 55.2 56.3 58.1 60.1 62.2 64.0 65.2 Height (cm) 140.3 143.0 147.5 152.7 157.9 162.6 165.5 140.3 143.0 147.5 152.7 157.9 162.6 165.5 50th 101 101 102 104 106 108 109 61 62 62 62 62 63 63 90th 113 114 115 117 119 121 122 75 75 75 75 75 76 76 95th 116 117 118 121 124 126 128 78 78 78 78 78 79 79 95th + 12 mmHg 128 129 130 133 136 138 140 90 90 90 90 90 91 91 13 years Height (in) 57.9 59.1 61.0 63.1 65.2 67.1 68.3 57.9 59.1 61.0 63.1 65.2 67.1 68.3 Height (cm) 147.0 150.0 154.9 160.3 165.7 170.5 173.4 147.0 150.0 154.9 160.3 165.7 170.5 173.4 50th 103 104 105 108 110 111 112 61 60 61 62 63 64 65 90th 115 116 118 121 124 126 126 74 74 74 75 76 77 77 95th 119 120 122 125 128 130 131 78 78 78 78 80 81 81 95th + 12 mmHg 131 132 134 137 140 142 143 90 90 90 90 92 93 93 14 years Height (in) 60.6 61.8 63.8 65.9 68.0 69.8 70.9 60.6 61.8 63.8 65.9 68.0 69.8 70.9 Height (cm) 153.8 156.9 162.0 167.5 172.7 177.4 180.1 153.8 156.9 162.0 167.5 172.7 177.4 180.1 50th 105 106 109 111 112 113 113 60 60 62 64 65 66 67 90th 119 120 123 126 127 128 129 74 74 75 77 78 79 80 95th 123 125 127 130 132 133 134 77 78 79 81 82 83 84 95th + 12 mmHg 135 137 139 142 144 145 146 89 90 91 93 94 95 96 15 years Height (in) 62.6 63.8 65.7 67.8 69.8 71.5 72.5 62.6 63.8 65.7 67.8 69.8 71.5 72.5 Height (cm) 159.0 162.0 166.9 172.2 177.2 181.6 184.2 159.0 162.0 166.9 172.2 177.2 181.6 184.2 50th 108 110 112 113 114 114 114 61 62 64 65 66 67 68 90th 123 124 126 128 129 130 130 75 76 78 79 80 81 81 95th 127 129 131 132 134 135 135 78 79 81 83 84 85 85 95th + 12 mmHg 139 141 143 144 146 147 147 90 91 93 95 96 97 97 16 years Height (in) 63.8 64.9 66.8 68.8 70.7 72.4 73.4 63.8 64.9 66.8 68.8 70.7 72.4 73.4 Height (cm) 162.1 165.0 169.6 174.6 179.5 183.8 186.4 162.1 165.0 169.6 174.6 179.5 183.8 186.4 50th 111 112 114 115 115 116 116 63 64 66 67 68 69 69 90th 126 127 128 129 131 131 132 77 78 79 80 81 82 82 95th 130 131 133 134 135 136 137 80 81 83 84 85 86 86 95th + 12 mmHg 142 143 145 146 147 148 149 92 93 95 96 97 98 98 17 years Height (in) 64.5 65.5 67.3 69.2 71.1 72.8 73.8 64.5 65.5 67.3 69.2 71.1 72.8 73.8 Height (cm) 163.8 166.5 170.9 175.8 180.7 184.9 187.5 163.8 166.5 170.9 175.8 180.7 184.9 187.5 50th 114 115 116 117 117 118 118 65 66 67 68 69 70 70 90th 128 129 130 131 132 133 134 78 79 80 81 82 82 83 95th 132 133 134 135 137 138 138 81 82 84 85 86 86 87 95th + 12 mmHg 144 145 146 147 149 150 150 93 94 96 97 98 98 99The 50th, 90th, and 95th percentiles were derived by using quantile regression on the basis of normal-weight children (BMI <85th percentile). BP stages are defined as elevated BP ≥90th percentile but <95th percentile; stage 1 HTN: ≥95th percentile or 130/80 to 139/89 mmHg; and stage 2 HTN: ≥95th percentile + 12 mmHg or >140/90 mmHg.BP: blood pressure; BMI: body mass index; HTN: hypertension.Reproduced with permission from: Pediatrics, Vol. 140, doi: 10.1542/peds.2017-1904. Copyright © 2017 by the AAP.Graphic 63856 Version 18.0

CloseSensitivity and specificity of ultrasonography in the detection of Crohn disease (with respect to endoscopic, radiologic and operative findings)Sensitivity and specificity of ultrasonography in the detection of Crohn disease (with respect to endoscopic, radiologic and operative findings) Number of patients Sensitivity Specificity PPV NPV Study Author Year 181 (89) 81 79 79 81 [1] Pera A, et al 1988 61 (26) 77 96 NE NE [2] Stiatti A, et al 1990 36 86 97 NE NE [3] Hata J, et al 1992 127 (46) 78 (87)* 91 NE NE [4] Sheridan MB, et al 1993 (31) 73 93 NE NE [5] Brignola C, et al 1993 41 96 100 NE NE [6] Limberg B, et al 1994 59 95 93 90 95 [7] Solvig J, et al 1995 (115) 89 94 NE NE [8] Maconi G, et al 1996 227 (69) 84 NE 98 76 [9] Hollerbach S, et al 1998 (47) 81 86 96 57 [10] Andreoli A, et al 1998 30 87 100 NE NE [11] Miao YM, et al 2002 296 93 97 NE NE [12] Parente F, et al 2002 296 (211) 79 98 95 NE [12] Parente F, et al 2002 296 (85) 90 100 100 NE [12] Parente F, et al 2002 46 76 NE NE NE [13] Potthast S, et al 2002 46 31 NE NE NE [13] Potthast S, et al 2002 46 58 NE NE NE [13] Potthast S, et al 2002 46 89 NE NE NE [13] Potthast S, et al 2002 78 77 83 NE NE [14] Haber HP, et al 2002 48 56 97 NE NE [15] Schmidt T, et al 2003 48 56 97 NE NE [15] Schmidt T, et al 2003 48 67 100 NE NE [15] Schmidt T, et al 2003 625 (128) 87 96 93 81 [16] Maconi G, et al 2003 625 (128) 91 85 77 94 [16] Maconi G, et al 2003 102 91/96¶ NE NE NE [17] Parente F, et al 2004 102 74/89¶ 97 92 96 [17] Parente F, et al 2004 84 (50) 92 97 98 88 [18] Rispo A, et al 2005 48 81Δ 63Δ 63Δ 81Δ [19] Serra C, et al 2007 53 85◊ NE NE NE [20] Maconi G, et al 2007 119 91 NE NE NE [21] Martinez MJ, et al 2009 119 80 NE NE NE [21] Martinez MJ, et al 2009 58 86 90 83 92 [22] Neye H, et al 2010 58 78 95 86 91 [22] Neye H, et al 2010 58 90 99 90 99 [22] Neye H, et al 2010 143 93 99 98  95  [23] Chatu S, et al 2012 15 92§/100¥/60‡/100† 0§/50¥/88‡/80† NE NE [24] Onali S, et al 2012 49  96‡/100†  91‡/95† NE NE [25] Pallotta N, et al  2012 59 98**/83¶¶  67**/98¶¶ NE NE [26] Calabrese E, et al  2013 PPV: positive predictive value; NPV: negative predictive value; NE: not evaluable. Parentheses indicate the number of patients with proven Crohn disease, if noted.* Learning curve.¶ Oral contrast-enhanced ultrasound.Δ Contrast-enhanced ultrasound.◊ Transperineal ultrasound.§ Strictures.¥ Dilation.‡ Fistulas.† Abscesses.** Small bowel.¶¶ Colon.References: Pera A, Cammarota T, Comino E, Caldera D, Ponti V, Astegiano M et al. Ultrasonography in the detection of Crohn's disease and in the differential diagnosis of inflammatory bowel disease. Digestion 1988; 41:180.Stiatti A, Martinuzzi A, Bartolini M, Lascialfari L, Trallori G, Morettini A. Ultrasonography in the diagnosis of chronic inflammatory intestinal disease. Radiol Med (Torino) 1990; 80:301.Hata J, Haruma K, Suenaga K, Yoshihara M, Yamamoto G, Tanaka S et al. Ultrasonographic assessment of inflammatory bowel disease. Am J Gastroenterol 1992; 87:443.Sheridan MB, Nicholson DA, Martin DF. Transabdominal ultrasonography as the primary investigation in patients with suspected Crohn's disease or recurrence: a prospective study. Clin Radiol 1993; 48:402.Brignola C, Belloli C, Iannone P, De Simone G, Corbelli C, Levorato M et al. Comparison of scintigraphy with indium-111 leukocyte scan and ultrasonography in assessment of X-ray-demonstrated lesions of Crohn's disease. Dig Dis Sci 1993; 38:433.Limberg B, Osswald B. Diagnosis and differential diagnosis of ulcerative colitis and Crohn's disease by hydrocolonic sonography. Am J Gastroenterol 1994; 89:1051.Solvig J, Ekberg O, Lindgren S, Floren CH, Nilsson P. Ultrasound examination of the small bowel: comparison with enteroclysis in patients with Crohn disease. Abdom Imaging 1995; 20:323.Maconi G, Parente F, Bollani S, Cesana B, Bianchi PG. Abdominal ultrasound in the assessment of extent and activity of Crohn's disease: clinical significance and implication of bowel wall thickening. Am J Gastroenterol 1996; 91:1604.Hollerbach S, Geissler A, Schiegl H, Kullmann F, Lock G, Schmidt J et al. The accuracy of abdominal ultrasound in the assessment of bowel disorders. Scand J Gastroenterol 1998; 33:1201.Andreoli A, Cerro P, Falasco G, Giglio LA, Prantera C. Role of ultrasonography in the diagnosis of postsurgical recurrence of Crohn's disease. Am J Gastroenterol 1998; 93:1117.Miao YM, Koh DM, Amin Z, Healy JC, Chinn RJ, Zeegen R et al. Ultrasound and magnetic resonance imaging assessmentof active bowel segments in Crohn's disease. Clin Radiol 2002; 57:913.Parente F, Maconi G, Bollani S, Anderloni A, Sampietro G, Cristaldi M et al. Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings. Gut 2002; 50:490.Potthast S, Rieber A, Von Tirpitz C, Wruk D, Adler G, Brambs HJ. Ultrasound and magnetic resonance imaging in Crohn's disease: a comparison. Eur Radiol 2002; 12:1416.Haber HP, Busch A, Ziebach R, Dette S, Ruck P, Stern M. Ultrasonographic findings correspond to clinical, endoscopic, and histologic findings in inflammatory bowel disease and other enterocolitides. J Ultrasound Med 2002; 21:375.Schmidt T, Reinshagen M, Brambs HJ, Adler G, Rieber A, Tirpitz V et al. Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease. Z Gastroenterol 2003; 41:641.Maconi G, Sampietro GM, Parente F, Pompili G, Russo A, Cristaldi M et al. Contrast radiology, computed tomography and ultrasonography in detecting internal fistulas and intra-abdominal abscesses in Crohn's disease: a prospective comparative study. Am J Gastroenterol 2003; 98:1545.Parente F, Greco S, Molteni M, Anderloni A, Sampietro GM, Danelli PG et al. Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy. Gut 2004; 53:1652.Rispo A, Imbriaco M, Celentano L, Cozzolino A, Camera L, Mainenti PP et al. Noninvasive diagnosis of small bowel Crohn's disease: combined use of bowel sonography and Tc-99m-HMPAO leukocyte scintigraphy. Inflamm Bowel Dis 2005; 11:376.Serra C, Menozzi G, Labate AM, Giangregorio F, Gionchetti P, Beltrami M, Robotti D, Fornari F, Cammarota T. Ultrasound assessment of vascularization of the thickened terminal ileum wall in Crohn's disease patients using a low-mechanical index real-time scanning technique with a second generation ultrasound contrast agent. Eur J Radiol. 2007; 62:114.Maconi G, Ardizzone S, Greco S, Radice E, Bezzio C, Bianchi Porro G. Transperineal ultrasound in the detection of perianal and rectovagin*l fistulae in Crohn's disease. Am J Gastroenterol. 2007; 102:2214.Martínez MJ, Ripollés T, Paredes JM, Blanc E, Martí-Bonmatí L. Assessment of the extension and the inflammatory activity in Crohn's disease: comparison of ultrasound and MRI. Abdom Imaging. 2009; 34:141.Neye H, Ensberg D, Rauh P, Peitz U, Mönkemüller K, Treiber G, Klauck S, Malfertheiner P, Rickes S. Impact of high-resolution transabdominal ultrasound in the diagnosis of complications of Crohn's disease. Scand J Gastroenterol. 2010; 45: 690.Chatu S, Pilcher J, Saxena Sk, et al. Diagnostic accuracy of small intestine ultrasonography using an oral contrast agent in Crohn's disease: comparative study from the UK. Clin Radiol 2012; 67:553.Onali S, Calabrese E, Petruzziello C, et al. Small intestine contrast ultrasonography vs computed tomography enteroclysis for assessing ileal Crohn's disease. World J Gastroenterol 2012; 18:6088.Pallotta N, Vincoli G, Montesani C, et al. Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in crohn's disease: a prospective comparative study versus intraoperative findings. Inflamm Bowel Dis 2012; 18:74.Calabrese E, Zorzi F, Onali S, et al. Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn's disease. Clin Gastroenterol Hepatol 2013; 11:950.Graphic 80268 Version 4.0

CloseNormal reference ranges in pregnancyNormal reference ranges in pregnancy   Nonpregnant females* First trimester Second trimester Third trimester References Hematology Erythropoietin¶ (units/L) 4 to 27 12 to 25 8 to 67 14 to 222 1-3,105 Ferritin¶ (ng/mL) 10 to 150Δ 6 to 130 2 to 230 0 to 116 1-8 Folate, red blood cell (ng/mL) 150 to 450 137 to 589 94 to 828 109 to 663 6, 9, 10 Folate, serum (ng/mL) 5.4 to 18.0 2.6 to 15.0 0.8 to 24.0 1.4 to 20.7 1, 6, 9-13 Haptoglobin (mg/mL) 25 to 250 130±43 115±50 135±65 91 Hemoglobin¶ (g/dL) 12 to 15.8Δ 11.6 to 13.9 9.7 to 14.8 9.5 to 15.0 2, 3, 6, 7, 13 Hematocrit¶ (%) 35.4 to 44.4 31.0 to 41.0 30.0 to 39.0 28.0 to 40.0 1, 2, 5, 6, 13-15 Iron, total binding capacity¶ (mcg/dL) 251 to 406 278 to 403 Not reported 359 to 609 7 Iron, serum¶ (mcg/dL) 41 to 141 72 to 143 44 to 178 30 to 193 2, 7 Mean corpuscular hemoglobin (pg/cell) 27 to 32 30 to 32 30 to 33 29 to 32 5 Mean corpuscular volume (xm3) 79 to 93 81 to 96 82 to 97 81 to 99 103 Platelet (x109/L) 165 to 415 174 to 391 155 to 409 146 to 429 5, 6, 14, 16, 17 Mean platelet volume (mcm3) 6.4 to 11.0 7.7 to 10.3 7.8 to 10.2 8.2 to 10.4 5 Red blood cell count (x106/mm3) 4.00 to 5.20Δ 3.42 to 4.55 2.81 to 4.49 2.71 to 4.43 5, 6, 13, 14 Red cell distribution width (%) <14.5 12.5 to 14.1 13.4 to 13.6 12.7 to 15.3 5 White blood cell count (x103/mm3) 3.5 to 9.1 5.7 to 13.6 5.6 to 14.8 5.9 to 16.9 5, 6, 13, 14, 18 Neutrophils (x103/mm3) 1.4 to 4.6 3.6 to 10.1 3.8 to 12.3 3.9 to 13.1 5, 14, 16, 18 Lymphocytes (×103/mm3) 0.7 to 4.6 1.1 to 3.6 0.9 to 3.9 1.0 to 3.6 5, 14, 16, 18 Monocytes (×103/mm3) 0.1 to 0.7 0.1 to 1.1 0.1 to 1.1 0.1 to 1.4 5, 14, 18 Eosinophils (×103/mm3) 0 to 0.6 0 to 0.6 0 to 0.6 0 to 0.6 14, 18 Basophils (×103/mm3) 0 to 0.2 0 to 0.1 0 to 0.1 0 to 0.1 14, 18 Transferrin (mg/dL) 200 to 400 254 to 344 220 to 441 288 to 530 4, 5 Transferrin, saturation without iron (%) 22 to 46¶ Not reported 10 to 44 5 to 37 3 Transferrin, saturation with iron (%) 22 to 46¶ Not reported 18 to 92 9 to 98 3 Hepcidin (ng/mL) Not reported 4 to 97 6 to 36 1 to 43 98, 100 Coagulation Antithrombin, functional (%) 70 to 130 89 to 114 78 to 126 82 to 116 17, 19, 20 Factor V (%) 50 to 150 75 to 95 72 to 96 60 to 88 25 Factor VII (%) 50 to 150 100 to 146 95 to 153 149 to 211 17 Factor VIII (%) 50 to 150 90 to 210 97 to 312 143 to 353 17, 25 Factor IX (%) 50 to 150 103 to 172 154 to 217 164 to 235 17 Factor XI (%) 50 to 150 80 to 127 82 to 144 65 to 123 17 Factor XII (%) 50 to 150 78 to 124 90 to 151 129 to 194 17 Fibrinogen (mg/dL) 211 to 496 244 to 510 291 to 538 301 to 696 5, 17, 20, 21, 23, 24, 85 hom*ocysteine (mmol/L) 4.4 to 10.8 3.34 to 11 2.0 to 26.9 3.2 to 21.4 6, 9, 10-12 International Normalized Ratio 0.9 to 1.04◊ 0.86 to 1.08 0.83 to 1.02 0.80 to 1.09 19, 24 Partial thromboplastin time, activated (seconds) 26.3 to 39.4 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0 5, 17, 19, 24 Plasminogen activator inhibitor-1 (PAI-1) antigen (pg/mL) 17.3±5.7 17.7±1.9 Not reported 66.4±4.9 85 Plasminogen activator inhibitor-1 (PAI-1) activity (arbitrary units) 9.3±1.9 9.0±0.8 Not reported 31.4±3.0 85 Prothrombin time (seconds) 12.7 to 15.4 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9 5, 17, 24 Protein C, functional (%) 70 to 130 78 to 121 83 to 133 67 to 135 19, 25, 26 Protein S, total (%) 70 to 140 39 to 105 27 to 101 33 to 101 17, 25, 26 Protein S, free (%) 70 to 140 34 to 133 19 to 113 20 to 65 25, 26 Protein S, functional activity (%) 65 to 140 57 to 95 42 to 68 16 to 42 25 Tissue plasminogen activator (ng/mL) 1.6 to 13§ 1.8 to 6.0 2.36 to 6.6 3.34 to 9.20 17, 19, 85 Tissue plasminogen activator inhibitor-1 (ng/mL) 4 to 43 16 to 33 36 to 55 67 to 92 17 Activated protein C resistance (APC-r) 2.12 to 5.00 1.79 to 4.75 1.00 to 2.83 1.61 to 5.00 104 D-Dimer (DDU) (ng/mL) <500 200 to 900 200 to 1600 400 to 500 21-23, 97 von Willebrand measurements von Willebrand factor antigen (%) 75 to 125 62 to 318 90 to 247 84 to 422 20, 27, 28 ADAMTS-13, von Willebrand cleaving protease 40 to 170¥ 40 to 160 22 to 135 38 to 105 20, 28 Blood chemical constituents Alanine transaminase (units/L) 7 to 41 3 to 30 2 to 33 2 to 25 4, 5, 8, 29 Albumin (g/dL) 4.1 to 5.3Δ 3.1 to 5.1 2.6 to 4.5 2.3 to 4.2 29-32 Alkaline phosphatase (units/L) 33 to 96 17 to 88 25 to 126 38 to 229 4, 5, 8, 29, 30 Alpha-1 antitrypsin (mg/dL) 100 to 200 225 to 323 273 to 391 327 to 487 5 Alpha-fetoprotein (ng/mL) — — Approximately 130-400 Approximately 130-590 93 Ammonia (microM) 31±3.2 — — 27.3±1.6 92 Amylase (units/L) 20 to 96 24 to 83 16 to 73 15 to 81 4, 5, 33, 34 Anion gap (mmol/L) 7 to 16 13 to 17 12 to 16 12 to 16 5 Aspartate transaminase (units/L) 12 to 38 3 to 23 3 to 33 4 to 32 4, 5, 8, 29 Bicarbonate (mmol/L) 22 to 30 20 to 24 20 to 24 20 to 24 5 Bilirubin, total (mg/dL) 0.3 to 1.3 0.1 to 0.4 0.1 to 0.8 0.1 to 1.1 4, 29, 99 Bilirubin, unconjugated (mg/dL) 0.2 to 0.9 0.1 to 0.5 0.1 to 0.4 0.1 to 0.5 5, 29 Bilirubin, conjugated (mg/dL) 0.1 to 0.4 0 to 0.1 0 to 0.1 0 to 0.1 29 Bile acids (micromol/L) 0.3 to 4.8‡ 0 to 4.9 0 to 9.1 0 to 11.3 29, 35 CA 125 antigen (units/mL) 7.2 to 27.0 2/2 to 268 12 to 25.1 16.8 to 43.8 86, 87, 88 Calcium, ionized (mg/dL) 4.5 to 5.3 4.5 to 5.1 4.4 to 5.0 4.4 to 5.3 5, 31, 36, 37 Calcium, total (mg/dL) 8.7 to 10.2 8.8 to 10.6 8.2 to 9.0 8.2 to 9.7 4, 5, 30, 32, 36-38 Ceruloplasmin (mg/dL) 25 to 63 30 to 49 40 to 53 43 to 78 5, 39 Chloride (mEq/L) 102 to 109 101 to 105 97 to 109 97 to 109 4, 5, 40 Creatinine (mg/dL) 0.5 to 0.9Δ 0.4 to 0.7 0.4 to 0.8 0.4 to 0.9 4, 5, 46 Gamma-glutamyl transpeptidase (units/L) 9 to 58 2 to 23 4 to 22 3 to 26 4, 5, 8, 29 Lactate dehydrogenase (units/L) 115 to 221 78 to 433 80 to 447 82 to 524 4, 5, 32, 8 Lipase (units/L) 3 to 43 21 to 76 26 to 100 41 to 112 33 Magnesium (mg/dL) 1.5 to 2.3 1.6 to 2.2 1.5 to 2.2 1.1 to 2.2 4, 5, 30-32, 36, 38 Osmolality (mOsm/kg H20) 275 to 295 275 to 280 276 to 289 278 to 280 38, 41 Phosphate (mg/dL) 2.5 to 4.3 3.1 to 4.6 2.5 to 4.6 2.8 to 4.6 4, 5, 30, 31, 42 Potassium (mEq/L) 3.5 to 5.0 3.6 to 5.0 3.3 to 5.0 3.3 to 5.1 4, 5, 15, 31, 32, 38, 40 Prealbumin (mg/dL) 17 to 34 15 to 27 20 to 27 14 to 23 5 Protein, total (g/dL) 6.7 to 8.6 6.2 to 7.6 5.7 to 6.9 5.6 to 6.7 5, 31, 32 Sodium (mEq/L) 136 to 146 133 to 148 129 to 148 130 to 148 4, 5, 15, 31, 32, 38, 41 Urea nitrogen (mg/dL) 7 to 20 7 to 12 3 to 13 3 to 11 4, 5, 40 Uric acid (mg/dL) 2.5 to 5.6Δ 2.0 to 4.2 2.4 to 4.9 3.1 to 6.3 4, 5, 41 Metabolic and endocrine tests Aldosterone (ng/dL) 2 to 9 6 to 104 9 to 104 15 to 101 43, 44, 45 Angiotensin converting enzyme (units/L) 9 to 67 1 to 38 1 to 36 1 to 39 39, 46 Alpha-fetoprotein (ng/mL) 0 to 8.5 Not reported 50 to 425 50 to 590 82, 84 Cortisol (mcg/dL) 0 to 25 7 to 19 10 to 42 12 to 50 5, 45 Hemoglobin A1C (%) 4 to 6 4 to 6 4 to 6 4 to 7 36, 47, 48 Parathyroid hormone (pg/mL) 8 to 51 10 to 15 18 to 25 9 to 26 30 Parathyroid hormone-related protein (pmol/L) <1.3† 0.7 to 0.9 1.8 to 2.2 2.5 to 2.8 30 Renin, plasma activity (ng/mL/hour) 0.3 to 9.0† Not reported 7.5 to 54.0 5.9 to 58.8 40, 44Thyroid-stimulating hormone (milli-int. units/mL) [American Thyroid Association recommendation]** 0.34 to 4.25 0.60 to 3.40 0.37 to 3.60 0.38 to 4.04 4, 5, 49 0.1 to 2.5 0.2 to 3.0 0.3 to 3.0 83 Thyroxine-binding globulin (mg/dL) 1.3 to 3.0 1.8 to 3.2 2.8 to 4.0 2.6 to 4.2 5 Thyroxine, free (ng/dL) 0.8 to 1.7 0.8 to 1.2 0.6 to 1.0 0.5 to 0.8 5, 49 Thyroxine, total (mcg/dL) 5.4 to 11.7 6.5 to 10.1 7.5 to 10.3 6.3 to 9.7 5, 32 Triiodothyronine, free (pg/mL) 2.4 to 4.2 4.1 to 4.4 4.0 to 4.2 Not reported 49 Triiodothyronine, total (ng/dL) 77 to 135 97 to 149 117 to 169 123 to 162 5 Vitamins and minerals Copper (mcg/dL) 70 to 140 112 to 199 165 to 221 130 to 240 50, 51, 5 Selenium (mcg/L) 63 to 160 116 to 146 75 to 145 71 to 133 5, 50 Vitamin A (retinol) (mcg/dL) 20 to 100 32 to 47 35 to 44 29 to 42 5 Vitamin B12 (pg/mL) 279 to 966 118 to 438 130 to 656 99 to 526 6, 10 Vitamin C (ascorbic acid) (mg/dL) 0.4 to 1.0 Not reported Not reported 0.9 to 1.3 52 Vitamin D, 1,25-dihydroxy (pg/mL) 25 to 45 20 to 65 72 to 160 60 to 119 30, 36 Vitamin D, 24,25-dihydroxy (ng/mL) 0.5 to 5.0† 1.2 to 1.8 1.1 to 1.5 0.7 to 0.9 53 Vitamin D, 25-hydroxy (ng/mL) 14 to 80 18 to 27 10 to 22 10 to 18 30, 53 Vitamin E (α-tocopherol) (mcg/mL) 5 to 18 7 to 13 10 to 16 13 to 23 5 Zinc (mcg/dL) 75 to 120 57 to 88 51 to 80 50 to 77 5, 13, 50 Autoimmune and inflammatory mediators C3 complement (mg/dL) 83 to 177 62 to 98 73 to 103 77 to 111 5 C4 complement (mg/dL) 16 to 47 18 to 36 18 to 34 22 to 32 5 C-reactive protein (mg/L) 0.2 to 3.0 Not reported 0.4 to 20.3 0.4 to 8.1 54 Erythrocyte sedimentation rate (mm/hour) 0 to 20Δ 4 to 57 7 to 47 13 to 70 55 Immunoglobulin A (mg/dL) 70 to 350 95 to 243 99 to 237 112 to 250 5 Immunoglobulin G (mg/dL) 700 to 1700 981 to 1267 813 to 1131 678 to 990 5 Immunoglobulin M (mg/dL) 50 to 300 78 to 232 74 to 218 85 to 269 5 Sex hormones Dehydroepiandrosterone sulfate (mmol/L) 1.3 to 6.8† 2.0 to 16.5 0.9 to 7.8 0.8 to 6.5 56 Estradiol (pg/mL) <20 to 443Δ,¶¶ 188 to 2497 1278 to 7192 614 to 3460 56, 57 Progesterone (ng/mL) <1 to 20Δ 8 to 48   99 to 342 56, 57 Prolactin (ng/mL) 0 to 20 36 to 213 110 to 330 137 to 372 30, 47, 57, 58 Sex hormone binding globulin (nmol/L) 18 to 114Δ 39 to 131 214 to 717 216 to 724 56, 59 Testosterone (ng/dL) 6 to 86Δ 25.7 to 211.4 34.3 to 242.9 62.9 to 308.6 56 17-hydroxyprogesterone (nmol/L) 0.6 to 10.6Δ,† 5.2 to 28.5 5.2 to 28.5 15.5 to 84 56 Lipids Cholesterol, total (mg/dL) <200 141 to 210 176 to 299 219 to 349 5, 60-62 High-density lipoprotein cholesterol (mg/dL) 40 to 60 40 to 78 52 to 87 48 to 87 5, 60-63 Low-density lipoprotein cholesterol (mg/dL) <100 60 to 153 77 to 184 101 to 224 5, 60-63 Very-low-density lipoprotein cholesterol (mg/dL) 6 to 40† 10 to 18 13 to 23 21 to 36 62 Triglycerides (mg/dL) <150 40 to 159 75 to 382 131 to 453 4, 5, 60-63 Apolipoprotein A-I (mg/dL) 119 to 240 111 to 150 142 to 253 145 to 262 4, 47, 61 Apolipoprotein B (mg/dL) 52 to 163 58 to 81 66 to 188 85 to 238 4, 47, 61 Cardiac function Cardiac output (L/minute) 4.8 to 6.8 5.6 to 9.7 5.5 to 9.9 4.8 to 8.7 64, 65, 66, 67, 68 Cardiac index (L/min/m2) 2.6 to 4.2 3.2 to 4.6 3.1 to 4.7 2.5 to 4.4 65, 68 Stroke volume (mL) 79 to 90 77.5 to 107.6 70.3 to 107.6 54 to 99 65, 68, 69 Stroke index (mL/m2)   46 to 62 39 to 62 30 to 42 65 Systemic vascular resistance (dyns/cm5) 700 to 1600 747 to 1485 692 to 1201 1034 to 1201 65, 67, 70 Echocardiography Intraventricular septal dimension (cm) 0.7 to 0.9 0.63 to 0.83 0.65 to 0.85 0.66 to 0.9 68, 69, 70, 89, 90 Posterior ventricular wall dimension (cm) 0.75 to 0.9 0.56 to 0.8 0.59 to 0.9 0.59 to 0.9 68, 69, 70, 89, 90 Left ventricular mass (g) 116 to 143 108 to 167 115 to 150 128 to 162 68, 70, 89, 90 Left ventricular mass index 40 to 78 53 to 79 58 to 82 60 to 88 68, 70, 89, 90 E/A ratio 1.4 to 1.75 1.6 1.4 1.3 68, 70 Left ventricular diastolic diameter (cm) 4.3 to 4.8 4.3 to 4.6 4.4 to 4.9 5.1 69, 70 Left ventricular systolic diameter (cm) 2.8 to 3.1 2.8 to 2.9 2.8 to 3.4 2.8 to 3.3 69, 70 Left vent, fractional shortening (%) 35 to 36 35 to 37 3.5 35 to 36 69, 70 Left vent ejection fraction (%) 60 to 73 61 to 75 61 to 63 60 to 73 69, 70 Diastolic function Mitral E wave (m/second) 0.77±0.11 0.85±0.13 0.84±0.16 0.77±0.15 89, 90 Mitral A wave (m/second) 0.46±0.1 0.5±0.09 0.5±0.1 0.55±0.1 89, 90 Isovolumic relaxation time (m/second) 69±10 50±10 79±18 72±16 89, 90 Cardiac function (blood tests) Atrial natriuretic peptide (pg/mL) Not reported Not reported 28.1 to 70.1 Not reported 73 B-type natriuretic peptide (pg/mL) <167 (age- and gender-specific) 18.4 13.5 to 29.5 15.5 to 46 71, 72, 73, 95 Creatine kinase (units/L) 39 to 238Δ 27 to 83 25 to 75 13 to 101 5, 74 Creatine kinase-MB (units/L) <6ΔΔ — — 1.8 to 2.4 74 N-terminal pro-brain natriuretic peptide (pg/mL) 50±26 60±45 60±40 43±34 94 Troponin I (hs-TnI) 0 to 1.0 0 to 1.0 0 to 1.0 0 to 1.0 102 Blood gas pH 7.38 to 7.42 (arterial) 7.36 to 7.52 (venous) 7.40 to 7.52 (venous) 7.41 to 7.53 (venous) 31, 75 7.39 to 7.45 (arterial) PO2 (mmHg) 90 to 100 93 to 100 90 to 98 92 to 107 75, 76 PCO2 (mmHg) 38 to 42 Not reported Not reported 25 to 33 75 Bicarbonate (HCO3–) (mEq/L) 22 to 26 Not reported Not reported 16 to 22 75 Renal function tests Effective renal plasma flow (mL/minute) 492 to 696Δ,† 696 to 985 612 to 1170 595 to 945 77, 78 Glomerular filtration rate (GFR) (mL/minute) 106 to 132Δ 131 to 166 135 to 170 117 to 182 77, 78, 79 Filtration fraction (%) 16.9 to 24.7◊◊ 14.7 to 21.6 14.3 to 21.9 17.1 to 25.1 77, 78, 79 Osmolarity, urine (mOsm/kg) 500 to 800 326 to 975 278 to 1066 238 to 1034 80 24-h albumin excretion (mg/24 hours) <30 5 to 15 4 to 18 3 to 22 80, 81 24-h calcium excretion (mmol/24 hours) <7.5† 1.6 to 5.2 0.3 to 6.9 0.8 to 4.2 15 24-h creatinine clearance (mL/minute) 91 to 130 69 to 140 55 to 136 50 to 166 15, 78 24-h creatinine excretion (mmol/24 hours) 8.8 to 14† 10.6 to 11.6 10.3 to 11.5 10.2 to 11.4 80 24-h potassium excretion (mmol/24 hours) 25 to 100† 17 to 33 10 to 38 11 to 35 15 24-h protein excretion (mg/24 hours) <150 19 to 141 47 to 186 46 to 185 81 24-h sodium excretion (mmol/24 hours) 100 to 260† 53 to 215 34 to 213 37 to 149 15, 41 Pulmonary function tests Forced vital capacity (FVC) (L) 4.00±0.51 3.89±0.48 3.92±0.48 4.00±0.53 96 Forced expiratory volume in one second (FEV1) (L) 3.20±0.41 3.18±0.44 3.16±0.39 3.20±0.43 96 Peak expiratory flow (PEF) (L/second) 7.18±1.05 6.71±1.19 6.92±1.13 7.19±1.10 96 Tidal volume (L) 0.21 to 0.48 0.52±0.15 0.54±0.15 0.57±0.14 101 Minute ventilation (L) 2.27 to 10.35 12.63±3.89 13.05±3.55 14.08±4.07 101* Unless otherwise specified, all normal reference values are from the seventeenth edition of Harrison's Principles of Internal Medicine[82].¶ Range includes references with and without iron supplementation.Δ Normal reference range is specific range for females.◊ Reference values are from Cerneca et al: Coagulation and fibrinolysis changes in normal pregnancy increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis[19].§ References values are from Cerneca et al and Choi et al: Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy[17,19].¥ Reference values are from Mannuci et al: Changes in health and disease of the metalloprotease that cleaves von Willebrand factor[28].‡ Reference values are from Bacq Y et al: Liver function tests in normal pregnancy: a prospective study of 102 pregnant women and 102 matched controls[29].† Reference values are from the fifteenth edition of Harrison's Principles of Internal Medicine[83].** The American Thyroid Association recommends these TSH ranges if individual laboratories do not determine their own trimester-specific reference ranges.¶¶ Range is for premenopausal females and varies by menstrual cycle phase.ΔΔ Reference values are from Leiserowitz GS et al: Creatine 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Am J Obstet Gynecol 135:227, 1979 [PMID: 474676].Hwang HS, Kwon JY, Kim MA, et al: Maternal serum highly sensitive C-reactive protein in normal pregnancy and pre-eclampsia. Int J Gynecol Obstet 98:105, 2007 [PMID: 17588579].van den Broek NR, Letsky EA: Pregnancy and the erythrocyte sedimentation rate. Br J Obstet Gynaecol 108:1164, 2001.O'Leary P, Boyne P, Flett P, et al: Longitudinal assessment of changes in reproductive hormones during normal pregnancy. Clin Chem 35(5):667, 1991.Carranza-Lira S, Hernández F, Sánchez M, et al: Prolactin secretion in molar and normal pregnancy. Int J Gynaecol Obstet 60:137, 1998 [PMID: 9509951].Larrea F, Méndez I, Parra A: Serum pattern of different molecular forms of prolactin during normal human pregnancy. Hum Reprod 8:1617, 1993 [PMID: 8300816].Acromite MT, Mantzoros CS, Leach RE, et al: Androgens in preeclampsia. Am J Obstet Gynecol 180:60, 1999 [PMID: 9914579].Belo L, Caslake M, Gaffney D, et al: Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis 162:425, 2002 [PMID: 11996963].Desoye G, Schweditsch MO, Pfeiffer KP, et al: Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and postpartum. J Clin Endocrinol Metab 64:704, 1987 [PMID: 3546352].Jimenez DM, Pocovi M, Ramon-Cajal J, et al: Longitudinal study of plasma lipids and lipoprotein cholesterol in normal pregnancy and puerperium. Gynecol Obstet Invest 25:158, 1988 [PMID: 3391425].Piechota W, Staszewski A: Reference ranges of lipids and apolipoproteins in pregnancy. Eur J Obstet Gynecol Reprod Biol 45:27, 1992 [PMID: 1618359].Rang S, van Montfrans GA, Wolf H. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growth restriction. Am J Obstet Gynecol. 198(5):519.e1-9, 2008 PMID: 18279824.Moertl MG, Ulrich D, Pickel K, et al: Changes in haemodynamic and autonomous nervous system parameters measured non-invasively throughout normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 144 Suppl 1:S179-83. 2009 PMID: 19285779.Pandey Ak, Das A, Srinivas C, et al: Maternal myocardial performances in various stages of pregnancy and post-partum. Research Jour of Cardiology 3(1):9-16, 2010.Lees M. Central circulatory responses in normotensive and hypertensive pregnancy. Postgrad Med J. 55(643): 311–314, 1979. PMCID: PMC2425449.Poppas A, Shroff SG, Korcarz CE, et al: Serial assessment of the cardiovascular system in normal pregnancy: Role of arterial compliance and pulsatile arterial load. Circulation 95:2407-2415, 1997.Katz R, Karliner JS, Resnik R: Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects. Circulation 58: 434-441, 1978.Mesa A, Jessurun C, Hernandez A, et al: Left ventricular diastolic function in normal human pregnancy. Circulation 99:511-517, 1999.Resnik JL, Hong C, Resnik R, et al: Evaluation of B-type natriuetic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol 193:450-458, 2005.Hamid RR, Larsson A, Pernow J, et al: Assessment of left ventricular structure and function in preeclampsia by echocardiography and cardiovascular biomarkers. J Hypertens 27L2257-2264, 2009.Borghi CB, Esposti DD, Immordino V, et al: Relationship of systemic hemodynamics, left ventricular structure and function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia. Am J Obstet Gynecol 183:140, 2000 [PMID: 10920322].Leiserowitz GS, Evans AT, Samuels SJ, et al: Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period. J Reprod Med 37:910, 1992 [PMID: 1460608].Fadel HE, Northrop G, Misenhimer HR, et al: Acid-base determinations in amniotic fluid and blood of normal late pregnancy. Obstet Gynecol 53:99, 1979 [PMID: 32503].Spiropoulos K, Prodromaki E, Tsapanos V: Effect of body position on PaO2 and PaCO2 during pregnancy. Gynecol Obstet Invest 58:22, 2004 [PMID: 15028865].Dunlop W: Serial changes in renal haemodynamics during normal human pregnancy. Br J Obstet Gynaecol 88:1, 1981 [PMID: 7459285].Ezimokhai M, Davison JM, Philips PR, et al: Non-postural serial changes in renal function during the third trimester of normal human pregnancy. Br J Obstet Gynaecol 88:465, 1981 [PMID: 7236549].Moran P, Baylis PH, Lindheimer, et al: Glomerular ultrafiltration in normal and preeclamptic pregnancy. J Am Soc Nephrol 14:648, 2003 [PMID: 12595500].Risberg A, Larsson A, Olsson K, et al: Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre-eclampsia. Scand J Clin Lab Invest 64:17, 2004 [PMID: 15025425].Higby K, Suiter CR, Phelps JY, et al: Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 171:984, 1994 [PMID: 7943114].Kratz A, Pesce MA, Basner RC, Einstein AJ. Appendix: Laboratory values of clinical importance. In: Longo DL, Fauci AS, Kasper DL, et al (Eds). Harrison's Principles of Internal Medicine, 18th ed, McGraw-Hill, New York 2012. Appendix 1, p A-1.Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21:1081.Leek AE, Ruoss CF, Kitau MJ, Chard T. Magernal plasma alphafetoprotein levels in the second half of normal pregnancy: Relationship to fetal weight, and maternal age and parity. BJOG 1975; 82:669.Hale SA, Sobel B, Benvenuto A, et al. Coagulation and fibrinolytic system protein profiles in women with normal pregnancies and pregnancies complicated by hypertension. Pregnancy Hypertens 2012; 2:152.Spitzer M, Kaushal N, Benjamin F. Maternal CA-125 levels in pregnancy and the puerperium. J Reprod Med 1998; 43:387.Aslam N, Ong C, Woelfer B, et al. Serum CA-125 at 11-14 weeks of gestation in women with morphologically normal ovaries. BJOG 2000; 107:689.Jacobs IJ, Fay TN, Stabile I, et al. The distribution of CA 125 in the reproductive tract of pregnant and non-pregnant women. Br J Obstet Gynaecol 1988; 95:1190.Savu O, Jurcu? R, Giu?c? S, et al. Morphological and functional adaptation of the maternal heart during pregnancy. Circ Cardiovasc Imaging 2012; 5:289.Vitarelli A, Capotosto L. Role of echocardiography in the assessment and management of adult congenital heart disease in pregnancy. Int J Cardiovasc Imaging 2011; 27:843.Haram K, Augensen K, Elsayed S. Serum protein pattern in normal pregnancy with special reference to acute-phase reactants. BJOG 1983; 90:139.Jozwik M, Jozwik M, Pierzycki K, et al. Maternal and fetal blood ammonia concentrations in normal term human pregnancies. Biol Neonate 2005; 87:38.Leek AE, Ruoss CF, Kitau MG, et al. Maternal plasma alphafetoprotein levels in the second half of normal pregnancy: relationship to fetal weight and maternal age and parity. BJOG 1975; 82:669.Burlingame J, Hyeong JA, Tang WHW. Changes in cardiovascular biomarkers throughout pregnancy and the remote postpartum period. Am J Obstet Gynecol 2013; 208:S97.Burlingame JM, Yamasato K, Ahn HJ, et al. B-type natriuretic peptide and echocardiography reflect volume changes in pregnancy. J Perinatal Med 2017; 45:577.Grindheim G, Toska K, Estensen ME, et al. Changes in pulmonary function during pregnancy: a longitudinal cohort study. BJOG 2012; 119:94.Hedengran KK, Andersen MR, Stender S, et al. Large D-dimer fluctuation in normal pregnancy: A longitudinal cohort study of 4,117 samples from 714 healthy Danish women. Obstet Gynecol Int 2016; 2016:3561675.Hedengran KK, Nelson D, Anderson MR, et al. Hepcidin levels are low during pregnancy and increase around delivery in women without iron deficiency–a prospective cohort study. J Matern Fetal Neonatal Med 2016; 29:1506.Klajnbard A, Szecsi PB, Colov NP, et al. Laboratory reference intervals during pregnancy, delivery, and the early postpartum period. Clin Chem Lab Med 2010; 48:237.Koenig MD, Tussing-Humphreys L, Day J, et al. Hepcidin and iron homeostasis during pregnancy. Nutrients 2014; 6:3602.Kolarzyk E, Szot WM, Lyszczarz J. Lung function and breathing regulation parameters during pregnancy. Arch Gynecol Obstet 2005; 272: 53.Ravichandran J, Woon SY, Quek YS, et al. High-sensitivity cardiac troponin I levels in normal and hypertensive pregnancy. Am J Med 2019; 132:362.Reese JA, Peck JD, Deschamps DR, et al. Platelet counts during pregnancy. N Engl J Med 2018; 379:32.Paternoster DM, Stella A, Simoni P, et al. Activated protein C resistance in normal and pre-eclamptic pregnancies. Gynecol Obstet Invest 2002; 54:145.Wolfson GH, Vargas E, Browne VA, et al. Erythropoietin and Soluble Erythropoietin Receptor: A Role for Maternal Vascular Adaptation to High-Altitude Pregnancy. J Clin Endocrinol Metab 2017; 102:242.Modified and reproduced with permission from: Abbassi-Ghanavati M, Greer LG. Reference Table of Normal Laboratory Values in Uncomplicated Pregnancies. In: Cunningham FG, Leveno KJ, Bloom S, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics, 23rd Edition. New York: McGraw-Hill, 2010. Copyright © 2010 The McGraw-Hill Companies, Inc.Updated with information from: Abbassi-Ghanavati M, Greer LG. Reference Table of Normal Laboratory Values in Uncomplicated Pregnancies. In: Cunningham FG, Leveno KJ, Bloom S, Dashe JD, Hoffman BL, Casey BM, Spong CY. Williams Obstetrics, 25th Edition. New York: McGraw-Hill, 2018.Graphic 81137 Version 50.0

ClosePROSTQA model-predicted probabilities of men having functional erections suitable for intercourse two years after brachytherapy for prostate cancerPROSTQA model-predicted probabilities of men having functional erections suitable for intercourse two years after brachytherapy for prostate cancer Age, y Race/ethnicity* BMI¶ Predicted functional erections after treatment, percent (95% CI) (by pretreatment sexual HRQOL score)Δ 67 83 100 60 African American <25 78 (48-94) 92 (73-98) 98 (89-99) 25-<35 61 (35-83) 83 (62-94) 94 (83-98) ≥35 28 (7-69) 56 (18-88) 81 (41-96) White/other <25 54 (33-74) 79 (61-90) 93 (83-97) 25-<35 34 (22-48) 62 (50-73) 85 (75-91) ≥35 11 (3-37) 29 (9-63) 58 (24-86) 65 African American <25 73 (41-91) 89 (67-97) 97 (86-99) 25-<35 54 (28-77) 79 (54-92) 93 (77-98) ≥35 22 (5-62) 48 (14-84) 76 (33-95) White/other <25 46 (28-66) 73 (55-86) 90 (79-96) 25-<35 27 (18-39) 54 (44-65) 80 (69-88) ≥35 9 (2-30) 23 (6-56) 50 (18-82) 70 African American <25 66 (34-88) 86 (60-96) 95 (81-99) 25-<35 46 (21-73) 73 (45-90) 90 (70-97) ≥35 17 (3-56) 40 (10-80) 69 (25-94) White/other <25 39 (22-58) 67 (47-82) 87 (72-95) 25-<35 22 (13-33) 47 (34-60) 75 (60-86) ≥35 6 (1-25) 18 (4-50) 42 (13-78)PROSTQA: Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; BMI: body mass index; HRQOL: health-related quality of life.* White race/ethnicity included 3 percent of patients of other (non-African American) or unknown races/ethnicities.¶ Calculated as weight in kilograms divided by height in meters squared.Δ Specific values of pretreatment sexual functioning (Expanded Prostate Cancer Index Composite scores of 67, 83, and 100; range of 0-100, with a higher score representing better function) are tabulated to represent cohort distribution (25th, 50th, and 75th percentiles of scores among prostatectomy-treated patients) as well as to reflect a clinically relevant set of possible pretreatment sexual functioning. These values correspond to the 45th, 60th, and 85th percentiles among patients treated with brachytherapy. Across all treatment groups, these percentiles correspond to 358 patients (36 percent) with pretreatment sexual HRQOL scores of 67 or less, 441 (45 percent) with scores of 68-99, and 186 (19 percent) with scores of 100.Reproduced with permission from: Alemozaffar M, Regan MM, Cooperberg MR, et al. Prediction of erectile function following treatment for prostate cancer. JAMA 2011; 306:1205. Copyright © 2011 American Medical Association. All rights reserved.Graphic 82368 Version 19.0

ClosePsychometric properties of the M-CHAT-R and M-CHAT-R/FPsychometric properties of the M-CHAT-R and M-CHAT-R/F Test characteristic M-CHAT-R* M-CHAT-R/F¶ Sensitivity (95% CI) 91% (86-96) 85% (79-92) Specificity (95% CI) 96% (95-96) 99.3% (99-99) Negative predictive value 99.9% 99.99% Positive predictive value for ASD 14% 48% Positive predictive value for any developmental concern, including ASD (95% CI) Not reported 95% (92-98)M-CHAT-R: Modified Checklist for Autism in Toddlers, Revised; M-CHAT-R/F: MCHAT-R with follow-up interview; CI: confidence interval; ASD: autism spectrum disorder.* Total score of ≥3 on MCHAT-R with no follow-up interview.¶ Total score of ≥3 on MCHAT-R and ≥2 on the follow-up interview.Data from: Robins DL, Casagrande K, Barton M, et al. Validation of the Modified Checklist for Autism in Toddlers, Revised With Follow-up (M-CHAT-R/F). Pediatrics 2014; 133:37.Graphic 93751 Version 3.0

CloseSensitivities for various immunohistochemical markers in differentiating hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinomaSensitivities for various immunohistochemical markers in differentiating hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma   HCC CC MA Hep Par 1 86-96% 0-12.5% 0-14% GPC3 75-88% 0-19% 0-6% pCEA* 50-96% 100% 93-96% MOC 31 0-14% 67-100% 66-100% CK7 7-21% 78-100% 3-36% CK8/18 70% 20%   CK19 0-10% 44-80% 29-64% CK20 0-5% 10-11% 30-74% CD34¶ 94-95%    IHC: immunohistochemical; adenoCA: adenocarcinoma; HCC: hepatocellular carcinoma; CC: cholangiocarcinoma; MA: metastatic adenocarcinoma; Hep Par 1: hepatocyte paraffin 1; GPC3: glypican-3; pCEA: polyclonal carcinoembryonic antigen; CK: cytokeratin.* Positive pCEA staining is canalicular in HCC and membranous and/or cytoplasmic in CC and MA.¶ Positive CD34 staining is a complete/diffuse staining pattern of the sinusoidal endothelial cells.Original figure modified for this publication. Chan ES, Yeh MM. The use of immunohistochemistry in liver tumors. Clin Liver Dis 2010; 14:687. Table used with the permission of Elsevier Inc. All rights reserved.Graphic 97387 Version 1.0

ClosePrevention of infection with arterial cathetersPrevention of infection with arterial cathetersReplacement and relocation of catheter Do not routinely replace peripheral arterial catheters. Perform inspection of site daily for signs of infection, distal ischemia, or embolization. Replace disposable or reusable transducers at 96-hours intervals. Replace other components of the system, including tubing, continuous flush device, and flush solutions at the time the transducer is changed. Replacement of catheter-site dressing Replace dressing when the catheter is removed or replaced, or when the dressing becomes damp, loosened, or soiled. Replace dressings more frequently in diaphoretic patients. There is no need to remove a gauze or opaque dressing if the patient has no clinical signs of infection. Replacement of administration sets Replace the intravenous tubing, continuous flush device at the time the transducer is replaced (ie, 96-hour intervals). Hang time for parenteral fluids Replace the flush solution at the time the transducer is replaced (ie, 96-hour intervals).Graphic 65076 Version 4.0

Monotherapy with a single antiviral agent or interferon is unlikely to be sufficient for the eradication of hepatitis B virus (HBV) infection in the majority of patients who are chronically infected. With the availability of several medications, it is possible to contemplate combination therapy for

The treatment of human immunodeficiency virus (HIV) infection involves the use of combination antiretroviral therapy (ART). Use of these multidrug regimens substantially reduces progression to AIDS, opportunistic infections, hospitalizations, and death. Drug selection could potentially include more

CloseBlood pressure levels for females by age and height percentileBlood pressure levels for females by age and height percentile BP (percentile) Systolic BP (mmHg) Diastolic BP (mmHg) Height percentile or measured height Height percentile or measured height 5% 10% 25% 50% 75% 90% 95% 5% 10% 25% 50% 75% 90% 95% 1 year Height (in) 29.7 30.2 30.9 31.8 32.7 33.4 33.9 29.7 30.2 30.9 31.8 32.7 33.4 33.9 Height (cm) 75.4 76.6 78.6 80.8 83.0 84.9 86.1 75.4 76.6 78.6 80.8 83.0 84.9 86.1 50th 84 85 86 86 87 88 88 41 42 42 43 44 45 46 90th 98 99 99 100 101 102 102 54 55 56 56 57 58 58 95th 101 102 102 103 104 105 105 59 59 60 60 61 62 62 95th + 12 mmHg 113 114 114 115 116 117 117 71 71 72 72 73 74 74 2 years Height (in) 33.4 34.0 34.9 35.9 36.9 37.8 38.4 33.4 34.0 34.9 35.9 36.9 37.8 38.4 Height (cm) 84.9 86.3 88.6 91.1 93.7 96.0 97.4 84.9 86.3 88.6 91.1 93.7 96.0 97.4 50th 87 87 88 89 90 91 91 45 46 47 48 49 50 51 90th 101 101 102 103 104 105 106 58 58 59 60 61 62 62 95th 104 105 106 106 107 108 109 62 63 63 64 65 66 66 95th + 12 mmHg 116 117 118 118 119 120 121 74 75 75 76 77 78 78 3 years Height (in) 35.8 36.4 37.3 38.4 39.6 40.6 41.2 35.8 36.4 37.3 38.4 39.6 40.6 41.2 Height (cm) 91.0 92.4 94.9 97.6 100.5 103.1 104.6 91.0 92.4 94.9 97.6 100.5 103.1 104.6 50th 88 89 89 90 91 92 93 48 48 49 50 51 53 53 90th 102 103 104 104 105 106 107 60 61 61 62 63 64 65 95th 106 106 107 108 109 110 110 64 65 65 66 67 68 69 95th + 12 mmHg 118 118 119 120 121 122 122 76 77 77 78 79 80 81 4 years Height (in) 38.3 38.9 39.9 41.1 42.4 43.5 44.2 38.3 38.9 39.9 41.1 42.4 43.5 44.2 Height (cm) 97.2 98.8 101.4 104.5 107.6 110.5 112.2 97.2 98.8 101.4 104.5 107.6 110.5 112.2 50th 89 90 91 92 93 94 94 50 51 51 53 54 55 55 90th 103 104 105 106 107 108 108 62 63 64 65 66 67 67 95th 107 108 109 109 110 111 112 66 67 68 69 70 70 71 95th + 12 mmHg 119 120 121 121 122 123 124 78 79 80 81 82 82 83 5 years Height (in) 40.8 41.5 42.6 43.9 45.2 46.5 47.3 40.8 41.5 42.6 43.9 45.2 46.5 47.3 Height (cm) 103.6 105.3 108.2 111.5 114.9 118.1 120.0 103.6 105.3 108.2 111.5 114.9 118.1 120.0 50th 90 91 92 93 94 95 96 52 52 53 55 56 57 57 90th 104 105 106 107 108 109 110 64 65 66 67 68 69 70 95th 108 109 109 110 111 112 113 68 69 70 71 72 73 73 95th + 12 mmHg 120 121 121 122 123 124 125 80 81 82 83 84 85 85 6 years Height (in) 43.3 44.0 45.2 46.6 48.1 49.4 50.3 43.3 44.0 45.2 46.6 48.1 49.4 50.3 Height (cm) 110.0 111.8 114.9 118.4 122.1 125.6 127.7 110.0 111.8 114.9 118.4 122.1 125.6 127.7 50th 92 92 93 94 96 97 97 54 54 55 56 57 58 59 90th 105 106 107 108 109 110 111 67 67 68 69 70 71 71 95th 109 109 110 111 112 113 114 70 71 72 72 73 74 74 95th + 12 mmHg 121 121 122 123 124 125 126 82 83 84 84 85 86 86 7 years Height (in) 45.6 46.4 47.7 49.2 50.7 52.1 53.0 45.6 46.4 47.7 49.2 50.7 52.1 53.0 Height (cm) 115.9 117.8 121.1 124.9 128.8 132.5 134.7 115.9 117.8 121.1 124.9 128.8 132.5 134.7 50th 92 93 94 95 97 98 99 55 55 56 57 58 59 60 90th 106 106 107 109 110 111 112 68 68 69 70 71 72 72 95th 109 110 111 112 113 114 115 72 72 73 73 74 74 75 95th + 12 mmHg 121 122 123 124 125 126 127 84 84 85 85 86 86 87 8 years Height (in) 47.6 48.4 49.8 51.4 53.0 54.5 55.5 47.6 48.4 49.8 51.4 53.0 54.5 55.5 Height (cm) 121.0 123.0 126.5 130.6 134.7 138.5 140.9 121.0 123.0 126.5 130.6 134.7 138.5 140.9 50th 93 94 95 97 98 99 100 56 56 57 59 60 61 61 90th 107 107 108 110 111 112 113 69 70 71 72 72 73 73 95th 110 111 112 113 115 116 117 72 73 74 74 75 75 75 95th + 12 mmHg 122 123 124 125 127 128 129 84 85 86 86 87 87 87 9 years Height (in) 49.3 50.2 51.7 53.4 55.1 56.7 57.7 49.3 50.2 51.7 53.4 55.1 56.7 57.7 Height (cm) 125.3 127.6 131.3 135.6 140.1 144.1 146.6 125.3 127.6 131.3 135.6 140.1 144.1 146.6 50th 95 95 97 98 99 100 101 57 58 59 60 60 61 61 90th 108 108 109 111 112 113 114 71 71 72 73 73 73 73 95th 112 112 113 114 116 117 118 74 74 75 75 75 75 75 95th + 12 mmHg 124 124 125 126 128 129 130 86 86 87 87 87 87 87 10 years Height (in) 51.1 52.0 53.7 55.5 57.4 59.1 60.2 51.1 52.0 53.7 55.5 57.4 59.1 60.2 Height (cm) 129.7 132.2 136.3 141.0 145.8 150.2 152.8 129.7 132.2 136.3 141.0 145.8 150.2 152.8 50th 96 97 98 99 101 102 103 58 59 59 60 61 61 62 90th 109 110 111 112 113 115 116 72 73 73 73 73 73 73 95th 113 114 114 116 117 119 120 75 75 76 76 76 76 76 95th + 12 mmHg 125 126 126 128 129 131 132 87 87 88 88 88 88 88 11 years Height (in) 53.4 54.5 56.2 58.2 60.2 61.9 63.0 53.4 54.5 56.2 58.2 60.2 61.9 63.0 Height (cm) 135.6 138.3 142.8 147.8 152.8 157.3 160.0 135.6 138.3 142.8 147.8 152.8 157.3 160.0 50th 98 99 101 102 104 105 106 60 60 60 61 62 63 64 90th 111 112 113 114 116 118 120 74 74 74 74 74 75 75 95th 115 116 117 118 120 123 124 76 77 77 77 77 77 77 95th + 12 mmHg 127 128 129 130 132 135 136 88 89 89 89 89 89 89 12 years Height (in) 56.2 57.3 59.0 60.9 62.8 64.5 65.5 56.2 57.3 59.0 60.9 62.8 64.5 65.5 Height (cm) 142.8 145.5 149.9 154.8 159.6 163.8 166.4 142.8 145.5 149.9 154.8 159.6 163.8 166.4 50th 102 102 104 105 107 108 108 61 61 61 62 64 65 65 90th 114 115 116 118 120 122 122 75 75 75 75 76 76 76 95th 118 119 120 122 124 125 126 78 78 78 78 79 79 79 95th + 12 mmHg 130 131 132 134 136 137 138 90 90 90 90 91 91 91 13 years Height (in) 58.3 59.3 60.9 62.7 64.5 66.1 67.0 58.3 59.3 60.9 62.7 64.5 66.1 67.0 Height (cm) 148.1 150.6 154.7 159.2 163.7 167.8 170.2 148.1 150.6 154.7 159.2 163.7 167.8 170.2 50th 104 105 106 107 108 108 109 62 62 63 64 65 65 66 90th 116 117 119 121 122 123 123 75 75 75 76 76 76 76 95th 121 122 123 124 126 126 127 79 79 79 79 80 80 81 95th + 12 mmHg 133 134 135 136 138 138 139 91 91 91 91 92 92 93 14 years Height (in) 59.3 60.2 61.8 63.5 65.2 66.8 67.7 59.3 60.2 61.8 63.5 65.2 66.8 67.7 Height (cm) 150.6 153.0 156.9 161.3 165.7 169.7 172.1 150.6 153.0 156.9 161.3 165.7 169.7 172.1 50th 105 106 107 108 109 109 109 63 63 64 65 66 66 66 90th 118 118 120 122 123 123 123 76 76 76 76 77 77 77 95th 123 123 124 125 126 127 127 80 80 80 80 81 81 82 95th + 12 mmHg 135 135 136 137 138 139 139 92 92 92 92 93 93 94 15 years Height (in) 59.7 60.6 62.2 63.9 65.6 67.2 68.1 59.7 60.6 62.2 63.9 65.6 67.2 68.1 Height (cm) 151.7 154.0 157.9 162.3 166.7 170.6 173.0 151.7 154.0 157.9 162.3 166.7 170.6 173.0 50th 105 106 107 108 109 109 109 64 64 64 65 66 67 67 90th 118 119 121 122 123 123 124 76 76 76 77 77 78 78 95th 124 124 125 126 127 127 128 80 80 80 81 82 82 82 95th + 12 mmHg 136 136 137 138 139 139 140 92 92 92 93 94 94 94 16 years Height (in) 59.9 60.8 62.4 64.1 65.8 67.3 68.3 59.9 60.8 62.4 64.1 65.8 67.3 68.3 Height (cm) 152.1 154.5 158.4 162.8 167.1 171.1 173.4 152.1 154.5 158.4 162.8 167.1 171.1 173.4 50th 106 107 108 109 109 110 110 64 64 65 66 66 67 67 90th 119 120 122 123 124 124 124 76 76 76 77 78 78 78 95th 124 125 125 127 127 128 128 80 80 80 81 82 82 82 95th + 12 mmHg 136 137 137 139 139 140 140 92 92 92 93 94 94 94 17 years Height (in) 60.0 60.9 62.5 64.2 65.9 67.4 68.4 60.0 60.9 62.5 64.2 65.9 67.4 68.4 Height (cm) 154.4 154.7 158.7 163.0 167.4 171.3 173.7 154.4 154.7 158.7 163.0 167.4 171.3 173.7 50th 107 108 109 110 110 110 111 64 64 65 66 66 66 67 90th 120 121 123 124 124 125 125 76 76 77 77 78 78 78 95th 125 125 126 127 128 128 128 80 80 80 81 82 82 82 95th + 12 mmHg 137 137 138 139 140 140 140 92 92 92 93 94 94 94The 50th, 90th, and 95th percentiles were derived by using quantile regression on the basis of normal-weight children (BMI <85th percentile). BP stages are defined as elevated BP ≥90th percentile but <95th percentile; stage 1 HTN: ≥95th percentile or 130/80 to 139/89 mmHg; and stage 2 HTN: ≥95th percentile + 12 mmHg or >140/90 mmHg.BP: blood pressure; BMI: body mass index; HTN: hypertension.Reproduced with permission from: Pediatrics, Vol. 140, doi: 10.1542/peds.2017-1904. Copyright © 2017 by the AAP.Graphic 52646 Version 17.0

When thyroid nodule fine-needle aspiration (FNA) cytologic results show follicular lesion of undetermined significance or atypia of undetermined significance (FLUS/AUS, Bethesda III) or follicular neoplasm (Bethesda IV), the results are often called indeterminate. The risk of malignancy with these c

CloseTest characteristics of tests used to diagnose urinary tract infections in young infants (≤60 days)*Test characteristics of tests used to diagnose urinary tract infections in young infants (≤60 days)*   Sensitivity (95% CI) Specificity (95% CI) Positive likelihood ratio¶ (95% CI) Negative likelihood ratioΔ (95% CI) Leukocyte esterase (LE)◊ 92% (89-95%) 96% (95-96%) 21 (95% CIs not available) 0.08 (95% CIs not available) Nitrite 38% (33-44%) 99% (99-100%) 71 (95% CIs not available) 0.6 (95% CIs not available) LE or nitrite 93% (90-96%) 95% (95-96%) 19 (95% CIs not available) 0.07 (95% CIs not available) Pyuria (>5 WBC/hpf) 82% (77-86%) 94% (93-94%) 13 (95% CIs not available) 0.2 (95% CIs not available) LE or nitrite or pyuria 94% (91-97%) 91% (90-91%) 10.0 (9.0-11.1) 0.06 (0.04-0.1)CI: confidence interval; LE: leukocyte esterase; WBC: white blood cell; hpf: high-power field; UTI: urinary tract infection.* Results are based upon urine obtained by catheterization or suprapubic aspiration.¶ The positive likelihood ratio is the probability that an infant with a UTI will have a positive test divided by the probability that an infant without a UTI will have a positive test (eg, true-positive rate/false-positive rate). The higher the positive likelihood ratio, the better the test (a positive likelihood ratio >10 indicates excellent test performance; a perfect test would have a positive likelihood ration of infinity).Δ The negative likelihood ratio is the probability that an infant with a UTI will have a negative test divided by the probability that an infant without a UTI will have a negative test (eg, false-negative rate/true-negative rate). The lower the negative likelihood ratio, the better the test (a negative likelihood ratio <0.1 indicates excellent test performance; a perfect test has a negative likelihood ratio of 0).◊ This includes any positive LE result, including a trace amount.Adapted from: Tzimenatos L, Mahajan P, Dayan PS, et al. Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60 Days and Younger. Pediatrics 2018.Graphic 116587 Version 4.0

CloseRCVS2 score performanceRCVS2 score performance RCVS2 score Specificity Sensitivity PPV NPV Derivation cohort Score 5 or higher* 99 (93, 100) 90 (73, 98) 96 (82, 100) 96 (90, 99) Score 3 or 4* 86 (77, 93) 10 (2, 27) 21 (5, 51) 72 (62, 80) Score 2 or lower¶ 100 (88, 100) 85 (75, 92) 100 (95, 100) 71 (55, 84) Validation cohort Score 5 or higher* 94 (82, 99) 86 (80, 91) 98 (94, 100) 67 (54, 78) Score 3 or 4* 83 (69, 92) 11 (6, 17) 68 (46, 85) 22 (16, 28) Score 2 or lower¶ 96 (92, 99) 77 (62, 88) 86 (71, 95) 93 (88, 97)NPV: negative predictive value; PPV: positive predictive value; RCVS: reversible cerebral vasoconstriction syndrome.* Values for a RCVS diagnosis.¶ Values for a non-RCVS diagnosis.From: Rocha EA, Topcuoglu MA, Silva GS, Singhal AB. RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome. Neurology 2019; 92:e639. DOI: 10.1212/WNL.0000000000006917. Copyright © 2019 American Academy of Neurology. Reproduced with permission from Wolters Kluwer Health. Unauthorized reproduction of this material is prohibited.Graphic 121448 Version 2.0

CloseTypical initial settings for common modes of invasive mechanical ventilationTypical initial settings for common modes of invasive mechanical ventilation Setting Volume-limited Pressure-limited Notes Volume-limited assist control ventilation Synchronized intermitted mechanical ventilation with pressure support Pressure-limited assist control ventilation Tidal volume 6 mL/kg PBW 6 mL/kg PBW Inspiratory pressure is set to target an approximate desired tidal volume (refer below) Range is 6 to 8 mL/kg non-ARDS patients; 4 to 8 mL/kg ARDS patients. Ventilator rate 12 to 16 breaths per minute 12 to 16 breaths per minute 12 to 16 breaths per minute Higher rates may be necessary for patients with ARDS (eg, ≤35 breaths per minute). PEEP 5 to 10 cm H2O 5 to 10 cm H2O 5 to 10 cm H2O Lower levels are appropriate if an air leak is present and in patients who do not have ARDS (eg, 3 to 5 cm H2O); upward adjustment if hypoxemia from ARDS is severe. FiO2 FiO2 to target SpO2 90 to 96%* FiO2 to target SpO2 90 to 96%* FiO2 to target SpO2 90 to 96%* A lower limit may also be appropriate (eg, a PaO2 of 55 mmHg and an SpO2 of 88% in patients who are difficult to oxygenate or patients with hypercapnic hypoxemic respiratory failure. Higher limits may be necessary in certain conditions.¶ Inspiratory flow40 to 60 L per minute; ramp pattern Target an I:E ratio of 1:2 to 1:3Δ40 to 60 L per minute; ramp pattern Target an I:E ratio of 1:2 to 1:340 to 60 L per minute; ramp pattern Target an I:E ratio of 1:2 to 1:3 Higher rates up to 75 L per minute that increase the I:E ratio are appropriate in patients with airflow obstruction. Trigger sensitivity2 L/min (flow-triggered) –1 to –2 cm H2O (pressure triggered)2 L/min (flow-triggered) –1 to –2 cm H2O (pressure triggered)2 L/min (flow-triggered) –1 to –2 cm H2O (pressure triggered) Pressure triggering should not be used when auto-PEEP is suspected. PSV level N/A 5 to 10 cm H2O N/A PSV may be adjusted to target a desired tidal volume for unsupported breaths. Inspiratory pressure N/A N/A Variable (typically between 12 and 25 cm H2O) The initial inspiratory pressure varies depending upon lung compliance, airway resistance, and tubing resistance.PBW: predicted body weight (ie, ideal body weight); ARDS: acute respiratory distress syndrome; PEEP: positive end-expiratory pressure; FiO2: fraction of inspired oxygen; SpO2: peripheral oxygen saturation; PaO2: arterial oxygen tension; I:E ratio: inspiratory:expiratory ratio; N/A: not applicable; PSV: pressure support ventilation.* Patients are often started on an FiO2 of 1 immediately after intubation and weaned quickly over 30 minutes to reach the minimum FiO2 needed to achieve the target SpO2.¶ Conditions where higher FiO2 is indicated include carbon monoxide toxicity, cluster headaches, sickle cell crisis, pneumothorax, pregnancy, and air embolism.Δ Pressure-regulated volume-controlled ventilation sets an inspiratory time rather than setting the inspiratory flow to target the same I:E ratio.Graphic 123028 Version 3.0

CloseContaminant removal by water treatment systemContaminant removal by water treatment system Contaminant Component of the water treatment system used for removal Chemical contaminants with documented toxicity in hemodialysis patients Aluminum Reverse osmosis (60 to 99% removal) Copper Reverse osmosis (96 to 99% removal) Fluoride Reverse osmosis (80 to 99% removal) Lead Reverse osmosis (95 to 99% removal) Nitrate Reverse osmosis (90 to 95% removal) Sulfate Reverse osmosis (96 to 99% removal) Zinc Reverse osmosis (96 to 99% removal) Disinfectants added to water either municipally or locally with potential or documented toxicity in hemodialysis patients Chlorine and monochloramine Carbon filtration* Chlorine dioxide Hydrogen peroxide Silver-stabilized peroxide Peracetic acid Sodium hypochlorite (bleach) Trace elements regulated in drinking water with potential toxicity in hemodialysis patients Antimony Reverse osmosis (<90% removal) Arsenic Reverse osmosis (50 to 99% removal) Barium Reverse osmosis (99% removal) Beryllium Reverse osmosis (>90% removal) Cadmium Reverse osmosis (93 to 99% removal) Chromium Reverse osmosis (85 to 99% removal) Mercury Reverse osmosis (94 to 98% removal) Selenium¶ Reverse osmosis (99% removal) Silver¶ Reverse osmosis (93 to 97% removal) Thallium Reverse osmosis (>90% removal) Substances included in the hemodialysis fluid prescription Calcium Softener, reverse osmosis Magnesium Softener, reverse osmosis Potassium Reverse osmosis Sodium Reverse osmosis Microbial contaminants Bacteria Reverse osmosis, ultrafiltration, ultraviolet radiationΔ Endotoxin Reverse osmosis, ultrafiltration, ultraviolet radiationΔTypical rejection figures for reverse osmosis are based on thin film composite membranes. Rejection is dependent on the overall chemical profile of the water and the operating conditions (eg, pH and temperature). Different rejection rates can be achieved using a different system configuration (eg, double-stage reverse osmosis).* Effectiveness depends upon the disinfectant and the presence of other substances that might compete for binding or reaction sites.¶ Selenium and chromium levels in dialysis water are set at the "no-transfer" level.Δ Used in conjunction with a bacterial and endotoxin-retentive filter.Graphic 129916 Version 1.0

CloseLiposomal bupivacaine: Drug informationLiposomal bupivacaine: Drug information(For additional information see "Liposomal bupivacaine: Patient drug information" and see "Liposomal bupivacaine: Pediatric drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USExparelPharmacologic CategoryLocal AnestheticDosing: AdultNote: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.Analgesia, postsurgicalAnalgesia, postsurgical:Local anesthesia: Infiltration: Single dose: Dose is based on size of surgical site, volume required to cover the area, and individual patient factors (maximum dose: 266 mg [20 mL]). General dosage guidance for bunionectomy and hemorrhoidectomy provided below:Bunionectomy: 7 mL of undiluted bupivacaine (liposomal) infiltrated into the tissues surrounding the osteotomy and 1 mL of undiluted bupivacaine (liposomal) infiltrated into the subcutaneous tissue of the surgical site (total dose = 106 mg [8 mL])Hemorrhoidectomy: 30 mL of diluted bupivacaine (liposomal) (20 mL diluted with 10 mL NS) divided and infiltrated as 6 injections of 5 mL each (total dose = 266 mg [20 mL]) around the anal sphincter.Regional analgesia: Interscalene brachial plexus nerve block: Single dose:Total shoulder arthroplasty or rotator cuff repair: 133 mg (10 mL)Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling; renal impairment may reduce bupivacaine elimination increasing systemic exposure and the risk of adverse effects or toxicities; use with caution.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling; use with caution; severe impairment may reduce bupivacaine metabolism increasing systemic exposure and the risk of adverse effects or toxicities.Dosing: Pediatric(For additional information see "Liposomal bupivacaine: Pediatric drug information")Note: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.Local analgesiaLocal analgesia:Children ≥6 years and Adolescents <18 years: Local infiltration: 4 mg/kg administered once; maximum dose: 266 mg/dose (20 mL).Adolescents ≥18 years: Local infiltration: Single dose: Dose is based on size of surgical site, volume required to cover the area, and individual patient factors; maximum dose: 266 mg/dose (20 mL).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; renal impairment may reduce bupivacaine elimination, increasing systemic exposure and the risk of adverse effects or toxicities; use with caution and monitor closely.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor closely; severe impairment may reduce bupivacaine metabolism, increasing systemic exposure and the risk of adverse effects or toxicities.Dosing: Older AdultRefer to adult dosing.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suspension, Injection: Exparel: 1.3% (10 mL, 20 mL)Generic Equivalent Available: USNoAdministration: AdultAdminister undiluted or diluted. Inject slowly (1 to 2 mL per injection) into the surgical site using a ≥25 gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, or intra-articularly. Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection.Non-bupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; therefore, bupivacaine should be administered no sooner than 20 minutes after injection of lidocaine. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.Administration: PediatricParenteral: Local infiltration: Administer undiluted or diluted. Inject slowly (1 to 2 mL per injection) into the surgical site using a ≥25-gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, or intra-articularly. Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone-iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection.Nonbupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; therefore, bupivacaine (liposomal) should be administered no sooner than 20 minutes after injection of lidocaine. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.Use: Labeled IndicationsAnalgesia, postsurgical: Single-dose infiltration to produce postsurgical local analgesia in patients ≥6 years of age; interscalene brachial plexus nerve block to produce postsurgical regional analgesia in adults.Medication Safety IssuesSound-alike/look-alike issues:Bupivacaine may be confused with mepivacaine, ropivacaine Bupivacaine liposomal may be confused with conventional bupivacaineBupivacaine liposomal may be confused with propofol due to similar white, milky appearance.High alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error. Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%:Gastrointestinal: Constipation (2% to 22%), nausea (2% to 40%), vomiting (28%)Nervous system: Motor dysfunction (12% to 21%)Miscellaneous: Fever (2% to 23%)1% to 10%:Cardiovascular: Atrial fibrillation (<2%), bradycardia (1% to 2%), cardiac arrhythmia (<2%), deep vein thrombosis (<2%), edema (<2%), first degree atrioventricular block (<2%), hypertension (<10%), hypotension (7%), left bundle branch block (<2%), orthostatic hypotension (<2%), oxygen saturation decreased (<2%), palpitations (<2%), peripheral edema (2% to 3%), presyncope (<2%), prolonged QT interval on ECG (<2%), right bundle branch block (<2%), sinus bradycardia (<2%), sinus tachycardia (2% to 3%), supraventricular extrasystole (<2%), syncope (2%), tachycardia (3% to 4%), ventricular premature contractions (<2%), ventricular tachycardia (<2%)Dermatologic: Cellulitis (<2%), diaphoresis (<2%), erythema of skin (<2%), hyperhidrosis (5%), increased wound secretion (<2%), pallor (<2%), pruritic rash (<2%), pruritus (3%), skin blister (<2%), skin rash (<2%), urticaria (<2%)Gastrointestinal: Dysgeusia (7%), hiccups (1% to 2%), oral hypoesthesia (3% to 4%)Genitourinary: Dysuria (<2%), urinary incontinence (<2%), urinary retention (8%)Hematologic & oncologic: Anemia (6%, including acute posthemorrhagic anemia), hematoma (<2%), leukocytosis (<2%)Hepatic: Increased liver enzymes (4%), increased serum alanine aminotransferase (1%), increased serum aspartate aminotransferase (3%)Hypersensitivity: Fixed drug eruption (<2%), hypersensitivity reaction (<2%)Infection: Fungal infection (2%)Nervous system: Agitation (<2%), anxiety (3%), chills (<2%), confusion (5%), delirium (<2%), depression (<2%), dizziness (6%; includes postural dizziness), drowsiness (2% to 5%), fatigue (5%), feeling hot (2%), headache (4% to 8%), hyperthermia (<2%), hypoesthesia (2% to 4%), impaired mobility (decreased: 2%), insomnia (2% to 10%), lethargy (1%), myasthenia (<2%), pain (<2%), paresthesia (<2%), restlessness (<2%), sedated state (<2%), sensation disorder (sensory loss: 2%), sensation of cold (3%)Neuromuscular & skeletal: Arthralgia (<2%), asthenia (<2%), back pain (<10%), joint swelling (<2%), laryngospasm (<2%), muscle spasm (<10%), muscle twitching (8%), musculoskeletal pain (<2%), neck pain (<2%), tremor (<2%)Ophthalmic: Blurred vision (<2%), decreased visual acuity (<2%)Otic: Auditory impairment (<2%), tinnitus (<2%)Renal: Increased serum creatinine (2%)Respiratory: Apnea (<2%), atelectasis (<2%), cough (<2%), dyspnea (<2%), hypoxia (1% to 2%), pneumonia (<2%), pulmonary infection (<2%), pulmonary infiltrates (<2%), respiratory depression (<2%), respiratory failure (<2%)Postmarketing: Nervous system: Paralysis, seizureContraindicationsObstetrical paracervical block anesthesiaWarnings/PrecautionsConcerns related to adverse effects:• CNS effects: CNS effects (including excitation and/or depression) may occur, possibly leading to convulsions, unconsciousness, and/or respiratory arrest; may be related to total dose administered, route of administration, and physical status of patient; monitor for CNS-related changes or alterations in consciousness after each injection. Additionally, use of local anesthetics have been associated with neurologic effects following infiltration of soft tissue (persistent anesthesia, paresthesia weakness, paralysis), which may be irreversible.• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, twitching, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Sensory and/or motor loss is temporary and varies and may last up to 5 days.• Cardiovascular toxicity: Serious and fatal cardiovascular system reactions (eg, decreased cardiac output and arterial blood pressure, atrioventricular block, ventricular arrhythmias, cardiac arrest) may occur with toxic concentrations.• Hypersensitivity reactions: Allergic-type reactions (eg, angioneurotic edema [including laryngeal edema], dizziness, elevated temperature, excessive sweating, nausea, syncope, tachycardia, pruritus, erythema, sneezing, urticaria, vomiting) and possibly anaphylactoid-like symptoms (including severe hypotension) have been reported (rare); cross-sensitivity among amide-type local anesthetics has been reported.• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have been reported with local anesthetics.Disease-related concerns:• Cardiovascular disease: Use with caution in patients with cardiovascular disease; patients with impaired cardiovascular function are less able to compensate for functional changes associated with AV conduction prolongation produced by bupivacaine.• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with severe impairment may be at greater risk for toxicity.• Renal impairment: Use with caution in patients with renal impairment; may be at greater risk for toxicity.Other warnings/precautions:• Appropriate use: Avoid intravascular, epidural, intrathecal, and intra-articular nerve block injections. Not indicated for preincisional or preprocedural locoregional anesthetic techniques that require deep and complete sensory block. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration. Aspiration should be performed frequently prior to and during administration; the needle should be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.• Product interchangeability: Bupivacaine hydrochloride is not bioequivalent to bupivacaine (liposomal); dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) and vice versa is not possible.• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.Metabolism/Transport EffectsSubstrate of CYP1A2 (minor), CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Bupivacaine: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Risk D: Consider therapy modificationHyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Risk C: Monitor therapyLidocaine (Systemic): May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with lidocaine. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine. Lidocaine may be administered 96 hours or more after liposomal bupivacaine administration. Risk D: Consider therapy modificationLocal Anesthetics: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics, but may be administered 20 minutes or more after lidocaine. Avoid all local anesthetics within 96 hours after administration of liposomal bupivacaine. Risk X: Avoid combinationMethemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapyNeuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.Risk C: Monitor therapyTechnetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept.Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics.This interaction does not appear to apply to other uses of these agents in combination. Risk C: Monitor therapyPregnancy ConsiderationsBupivacaine crosses the placenta.Following use of the nonliposomal formulation, small amounts of bupivacaine can be found in the maternal plasma, potentially causing varying degrees of maternal, fetal, and neonatal toxicity involving the CNS, peripheral vascular tone, and cardiac function.Liposomal bupivacaine is approved for postsurgical local analgesia; studies have evaluated its use for intra-incisional blocks at the time of cesarean delivery to decrease postoperative pain (Parikh 2019; Prabhu 2018). Use of bupivacaine in obstetrical paracervical block anesthesia is contraindicated (may cause fetal bradycardia and death).Breastfeeding ConsiderationsBupivacaine and its active metabolite are present in breast milk.In order to evaluate breast milk concentrations of liposomal bupivacaine, a prospective cohort study was conducted in 30 women 18 to 40 years of age undergoing elective cesarean delivery between 37- and 42-weeks gestation. They received a bilateral transversus abdominis plane block under ultrasound guidance within 30 minutes of delivery using bupivacaine 52 mg and liposomal bupivacaine 266 mg.Maternal serum and breast milk were sampled over 96 hours. Bupivacaine was not present in milk samples collected prior to the transversus abdominis plane block. Peak concentrations of bupivacaine in breast milk occurred at 6 hours and were almost undetectable by 96 hours. Peak breast milk concentrations were 36% of the maternal plasma concentrations. Authors of the study calculated the relative infant dose to be <1% of the weight-adjusted maternal dose over the 96-hour dosing interval (<10% is considered compatible with breastfeeding). Adverse events (related or unrelated) were transient tachypnea noted in two neonates. There were no clinically significant adverse events in any of the neonates within the follow-up period of 14 days (Mustafa 2020).According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.Monitoring ParametersCardiovascular and respiratory (adequacy of ventilation) vital signs, state of consciousness; signs of CNS toxicity, pain relief.Mechanism of ActionBlocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction.Pharmaco*kineticsOnset: Rapid (Hu 2013)Duration: Local: Up to 72 hours (Hu 2013); Systemic: Plasma levels can persist for 96 hours after local administration and 120 hours after interscalene brachial plexus nerve block.Absorption: Systemic absorption varies; dependent on dose, route of administration, and vascularity of administration siteProtein binding: 95%Metabolism: Hepatic via conjugation; major metabolite pipecoloxylidine (PPX; inactive)Half-life elimination: 13 to 34 hours (Hu 2013)Time to peak, plasma: Within 1 hour (initial peak); 12 to 36 hours (second peak) (Hu 2013)Excretion: Urine (~6% unchanged)Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Renal impairment may reduce bupivacaine elimination increasing systemic exposure.Hepatic function impairment: Severe impairment may reduce bupivacaine metabolism increasing systemic exposure.Pricing: USSuspension (Exparel Injection)1.3% (per mL): $23.86Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.American College of Obstetricians and Gynecologists' (ACOG) Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 209: Obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. doi:10.1097/AOG.0000000000003132 [PubMed 30801474]Dix SK, Rosner GF, Nayar M, et al, “Intractable Cardiac Arrest Due to Lidocaine Toxicity Successfully Resuscitated With Lipid Emulsion,” Crit Care Med, 2011, 39(4):872-4. [PubMed 21263316]Exparel (bupivacaine liposomal) [prescribing information]. San Diego, CA: Pacira Pharmaceuticals Inc; March 2022.Golf M, Daniels SE, and Onel E, "A Phase 3, Randomized, Placebo-Controlled Trial of Depofoam® Bupivacaine (Extended-Release Bupivacaine Local Analgesic) in Bunionectomy," Adv Ther, 2011, 28(9):776-88. [PubMed 21842428]Gorfine SR, Onel E, Patou G, et al, "Bupivacaine Extended-Release Liposome Injection for Prolonged Postsurgical Analgesia in Patients Undergoing Hemorrhoidectomy: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial," Dis Colon Rectum, 2011, 54(12):1552-9. [PubMed 22067185]Hu D, Onel E, Singla N, Kramer WG, Hadzic A. Pharmaco*kinetic profile of liposome bupivacaine injection following a single administration at the surgical site. Clin Drug Investig. 2013;33(2):109-115. doi: 10.1007/s40261-012-0043-z. [PubMed 23229686]Mustafa HJ, Wong HL, Al-Kofahi M, Schaefer M, Karanam A, Todd MM. Bupivacaine pharmaco*kinetics and breast milk excretion of liposomal bupivacaine administered after cesarean birth. Obstet Gynecol. 2020;136(1):70-76. doi:10.1097/AOG.0000000000003886 [PubMed 32541292]Neal JM, Mulroy MF, and Weinberg GL, “American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2012 Version,” Reg Anesth Pain Med, 2012, 37(1):16-8. [PubMed 22189574]Parikh P, Sunesara I, Singh Multani S, Patterson B, Lutz E, Martin JN Jr. Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia: a retrospective study. J Matern Fetal Neonatal Med. 2019;32(6):966-970. doi:10.1080/14767058.2017.1397118 [PubMed 29065741]Prabhu M, Clapp MA, McQuaid-Hanson E, et al. Liposomal bupivacaine block at the time of cesarean delivery to decrease postoperative pain: a randomized controlled trial. Obstet Gynecol. 2018;132(1):70-78. doi:10.1097/AOG.0000000000002649 [PubMed 29889750]Topic 17057 Version 116.0

The goals of antiretroviral therapy (ART) are to reduce HIV-related morbidity and mortality (from both infectious and noninfectious causes) and to prevent transmission of HIV to others. For most treatment-naïve patients, ART regimens contains two different nucleoside reverse transcriptase inhibitors

CloseLiposomal bupivacaine: Pediatric drug informationLiposomal bupivacaine: Pediatric drug information(For additional information see "Liposomal bupivacaine: Drug information" and see "Liposomal bupivacaine: Patient drug information")For abbreviations, symbols, and age group definitions used in Lexicomp (show table)Brand Names: USExparelTherapeutic CategoryAnalgesic, NonopioidDosing: PediatricNote: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.Local analgesiaLocal analgesia:Children ≥6 years and Adolescents <18 years: Local infiltration: 4 mg/kg administered once; maximum dose: 266 mg/dose (20 mL).Adolescents ≥18 years: Local infiltration: Single dose: Dose is based on size of surgical site, volume required to cover the area, and individual patient factors; maximum dose: 266 mg/dose (20 mL).Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; renal impairment may reduce bupivacaine elimination, increasing systemic exposure and the risk of adverse effects or toxicities; use with caution and monitor closely.Dosing: Hepatic Impairment: PediatricThere are no dosage adjustments provided in the manufacturer's labeling; use with caution and monitor closely; severe impairment may reduce bupivacaine metabolism, increasing systemic exposure and the risk of adverse effects or toxicities.Dosing: Adult(For additional information see "Liposomal bupivacaine: Drug information")Note: Bupivacaine (liposomal) is not bioequivalent to bupivacaine hydrochloride; dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) or vice versa is not possible.Analgesia, postsurgicalAnalgesia, postsurgical:Local anesthesia: Infiltration: Single dose: Dose is based on size of surgical site, volume required to cover the area, and individual patient factors (maximum dose: 266 mg [20 mL]). General dosage guidance for bunionectomy and hemorrhoidectomy provided below:Bunionectomy: 7 mL of undiluted bupivacaine (liposomal) infiltrated into the tissues surrounding the osteotomy and 1 mL of undiluted bupivacaine (liposomal) infiltrated into the subcutaneous tissue of the surgical site (total dose = 106 mg [8 mL])Hemorrhoidectomy: 30 mL of diluted bupivacaine (liposomal) (20 mL diluted with 10 mL NS) divided and infiltrated as 6 injections of 5 mL each (total dose = 266 mg [20 mL]) around the anal sphincter.Regional analgesia: Interscalene brachial plexus nerve block: Single dose:Total shoulder arthroplasty or rotator cuff repair: 133 mg (10 mL)Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.Dosing: Kidney Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling; renal impairment may reduce bupivacaine elimination increasing systemic exposure and the risk of adverse effects or toxicities; use with caution.Dosing: Hepatic Impairment: AdultThere are no dosage adjustments provided in the manufacturer’s labeling; use with caution; severe impairment may reduce bupivacaine metabolism increasing systemic exposure and the risk of adverse effects or toxicities.Dosage Forms: USExcipient information presented when available (limited, particularly for generics); consult specific product labeling.Suspension, Injection: Exparel: 1.3% (10 mL, 20 mL)Generic Equivalent Available: USNoAdministration: PediatricParenteral: Local infiltration: Administer undiluted or diluted. Inject slowly (1 to 2 mL per injection) into the surgical site using a ≥25-gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, or intra-articularly. Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone-iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection.Nonbupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; therefore, bupivacaine (liposomal) should be administered no sooner than 20 minutes after injection of lidocaine. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.Administration: AdultAdminister undiluted or diluted. Inject slowly (1 to 2 mL per injection) into the surgical site using a ≥25 gauge needle with frequent aspiration prior to and during administration; do not filter. Do not administer epidurally, intrathecally, intravascularly, or intra-articularly. Do not allow bupivacaine (liposomal) to come into contact with antiseptics (eg, povidone iodine) in solution; when a topical antiseptic is applied, allow site to dry prior to injection.Non-bupivacaine-based local anesthetics may cause an immediate release of bupivacaine (liposomal) if administered together locally; therefore, bupivacaine should be administered no sooner than 20 minutes after injection of lidocaine. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration; bupivacaine hydrochloride may be administered simultaneously in the same syringe or injected immediately before bupivacaine (liposomal) as long as the milligram ratio of bupivacaine hydrochloride to bupivacaine (liposomal) does not exceed 1:2.Storage/StabilityStore intact vials at 2°C to 8°C (36°F to 46°F); may also store at 20°C to 25°C (68°F to 77°F) for up to 30 days (do not re-refrigerate); do not heat or autoclave vials before use. Following withdrawal from the vial, store at 20°C to 25°C (68°F to 77°F) up to 4 hours prior to administration. Diluted suspensions must be used within 4 hours of preparation. Do not freeze or expose to high temperature (>40°C [104°F]) for an extended period of time or administer if suspected of being frozen or exposed to high temperatures. Discard any unused portion.UseSingle-dose infiltration to produce postsurgical local analgesia (FDA approved in ages ≥6 years and adults); interscalene brachial plexus nerve block to produce postsurgical regional analgesia (FDA approved in adults).Medication Safety IssuesSound-alike/look-alike issues:Bupivacaine may be confused with mepivacaine, ropivacaine Bupivacaine liposomal may be confused with conventional bupivacaineBupivacaine liposomal may be confused with propofol due to similar white, milky appearance.High alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error. Adverse ReactionsThe following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.>10%:Gastrointestinal: Constipation (2% to 22%), nausea (2% to 40%), vomiting (28%)Nervous system: Motor dysfunction (12% to 21%)Miscellaneous: Fever (2% to 23%)1% to 10%:Cardiovascular: Atrial fibrillation (<2%), bradycardia (1% to 2%), cardiac arrhythmia (<2%), deep vein thrombosis (<2%), edema (<2%), first degree atrioventricular block (<2%), hypertension (<10%), hypotension (7%), left bundle branch block (<2%), orthostatic hypotension (<2%), oxygen saturation decreased (<2%), palpitations (<2%), peripheral edema (2% to 3%), presyncope (<2%), prolonged QT interval on ECG (<2%), right bundle branch block (<2%), sinus bradycardia (<2%), sinus tachycardia (2% to 3%), supraventricular extrasystole (<2%), syncope (2%), tachycardia (3% to 4%), ventricular premature contractions (<2%), ventricular tachycardia (<2%)Dermatologic: Cellulitis (<2%), diaphoresis (<2%), erythema of skin (<2%), hyperhidrosis (5%), increased wound secretion (<2%), pallor (<2%), pruritic rash (<2%), pruritus (3%), skin blister (<2%), skin rash (<2%), urticaria (<2%)Gastrointestinal: Dysgeusia (7%), hiccups (1% to 2%), oral hypoesthesia (3% to 4%)Genitourinary: Dysuria (<2%), urinary incontinence (<2%), urinary retention (8%)Hematologic & oncologic: Anemia (6%, including acute posthemorrhagic anemia), hematoma (<2%), leukocytosis (<2%)Hepatic: Increased liver enzymes (4%), increased serum alanine aminotransferase (1%), increased serum aspartate aminotransferase (3%)Hypersensitivity: Fixed drug eruption (<2%), hypersensitivity reaction (<2%)Infection: Fungal infection (2%)Nervous system: Agitation (<2%), anxiety (3%), chills (<2%), confusion (5%), delirium (<2%), depression (<2%), dizziness (6%; includes postural dizziness), drowsiness (2% to 5%), fatigue (5%), feeling hot (2%), headache (4% to 8%), hyperthermia (<2%), hypoesthesia (2% to 4%), impaired mobility (decreased: 2%), insomnia (2% to 10%), lethargy (1%), myasthenia (<2%), pain (<2%), paresthesia (<2%), restlessness (<2%), sedated state (<2%), sensation disorder (sensory loss: 2%), sensation of cold (3%)Neuromuscular & skeletal: Arthralgia (<2%), asthenia (<2%), back pain (<10%), joint swelling (<2%), laryngospasm (<2%), muscle spasm (<10%), muscle twitching (8%), musculoskeletal pain (<2%), neck pain (<2%), tremor (<2%)Ophthalmic: Blurred vision (<2%), decreased visual acuity (<2%)Otic: Auditory impairment (<2%), tinnitus (<2%)Renal: Increased serum creatinine (2%)Respiratory: Apnea (<2%), atelectasis (<2%), cough (<2%), dyspnea (<2%), hypoxia (1% to 2%), pneumonia (<2%), pulmonary infection (<2%), pulmonary infiltrates (<2%), respiratory depression (<2%), respiratory failure (<2%)Postmarketing: Nervous system: Paralysis, seizureContraindicationsObstetrical paracervical block anesthesiaWarnings/PrecautionsConcerns related to adverse effects:• CNS effects: CNS effects (including excitation and/or depression) may occur, possibly leading to convulsions, unconsciousness, and/or respiratory arrest; may be related to total dose administered, route of administration, and physical status of patient; monitor for CNS-related changes or alterations in consciousness after each injection. Additionally, use of local anesthetics have been associated with neurologic effects following infiltration of soft tissue (persistent anesthesia, paresthesia weakness, paralysis), which may be irreversible.• CNS toxicity: Careful and constant monitoring of the patient's state of consciousness should be done following each local anesthetic injection; at such times, restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, twitching, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of CNS toxicity. Sensory and/or motor loss is temporary and varies and may last up to 5 days.• Cardiovascular toxicity: Serious and fatal cardiovascular system reactions (eg, decreased cardiac output and arterial blood pressure, atrioventricular block, ventricular arrhythmias, cardiac arrest) may occur with toxic concentrations.• Hypersensitivity reactions: Allergic-type reactions (eg, angioneurotic edema [including laryngeal edema], dizziness, elevated temperature, excessive sweating, nausea, syncope, tachycardia, pruritus, erythema, sneezing, urticaria, vomiting) and possibly anaphylactoid-like symptoms (including severe hypotension) have been reported (rare); cross-sensitivity among amide-type local anesthetics has been reported.• Intra-articular infusion related chondrolysis: Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use; chondrolysis (primarily in the shoulder joint) has occurred following infusion, with some cases requiring arthroplasty or shoulder replacement.• Methemoglobinemia: Has been reported with local anesthetics; clinically significant methemoglobinemia requires immediate treatment along with discontinuation of the anesthetic and other oxidizing agents. Onset may be immediate or delayed (hours) after anesthetic exposure. Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, exposure to oxidizing agents or their metabolites, or infants <6 months of age are more susceptible and should be closely monitored for signs and symptoms of methemoglobinemia (eg, cyanosis, headache, rapid pulse, shortness of breath, lightheadedness, fatigue).• Respiratory arrest: Local anesthetics have been associated with rare occurrences of sudden respiratory arrest.• Seizures: Convulsions due to systemic toxicity leading to cardiac arrest have been reported with local anesthetics.Disease-related concerns:• Cardiovascular disease: Use with caution in patients with cardiovascular disease; patients with impaired cardiovascular function are less able to compensate for functional changes associated with AV conduction prolongation produced by bupivacaine.• Hepatic impairment: Use with caution in patients with hepatic impairment; patients with severe impairment may be at greater risk for toxicity.• Renal impairment: Use with caution in patients with renal impairment; may be at greater risk for toxicity.Other warnings/precautions:• Appropriate use: Avoid intravascular, epidural, intrathecal, and intra-articular nerve block injections. Not indicated for preincisional or preprocedural locoregional anesthetic techniques that require deep and complete sensory block. Do not administer other local anesthetics or other formulations of bupivacaine within 96 hours following bupivacaine (liposomal) administration. Aspiration should be performed frequently prior to and during administration; the needle should be repositioned until no return of blood can be elicited by aspiration; however, absence of blood in the syringe does not guarantee that intravascular injection has been avoided.• Product interchangeability: Bupivacaine hydrochloride is not bioequivalent to bupivacaine (liposomal); dosing conversion from bupivacaine hydrochloride to bupivacaine (liposomal) and vice versa is not possible.• Trained personnel: Clinicians using local anesthetic agents should be well trained in diagnosis and management of emergencies that may arise from the use of these agents. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use.Metabolism/Transport EffectsSubstrate of CYP1A2 (minor), CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potentialDrug InteractionsNote: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed).For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions programBupivacaine: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Bupivacaine may be administered immediately before, or administered in the same admixture syringe as liposomal bupivacaine as long as the ratio of the milligram dose of bupivacaine to liposomal bupivacaine does not exceed 1:2. Risk D: Consider therapy modificationHyaluronidase: May enhance the adverse/toxic effect of Local Anesthetics. Risk C: Monitor therapyLidocaine (Systemic): May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with lidocaine. Liposomal bupivacaine may be administered 20 minutes or more after the administration of lidocaine. Lidocaine may be administered 96 hours or more after liposomal bupivacaine administration. Risk D: Consider therapy modificationLocal Anesthetics: May enhance the adverse/toxic effect of Bupivacaine (Liposomal). Management: Liposomal bupivacaine should not be administered with local anesthetics, but may be administered 20 minutes or more after lidocaine. Avoid all local anesthetics within 96 hours after administration of liposomal bupivacaine. Risk X: Avoid combinationMethemoglobinemia Associated Agents: May enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapyNeuromuscular-Blocking Agents: Local Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.Risk C: Monitor therapyTechnetium Tc 99m Tilmanocept: Local Anesthetics may diminish the diagnostic effect of Technetium Tc 99m Tilmanocept.Management: Avoid mixing and simultaneously co-injecting technetium Tc 99m tilmanocept with local anesthetics.This interaction does not appear to apply to other uses of these agents in combination. Risk C: Monitor therapyPregnancy ConsiderationsBupivacaine crosses the placenta.Following use of the nonliposomal formulation, small amounts of bupivacaine can be found in the maternal plasma, potentially causing varying degrees of maternal, fetal, and neonatal toxicity involving the CNS, peripheral vascular tone, and cardiac function.Liposomal bupivacaine is approved for postsurgical local analgesia; studies have evaluated its use for intra-incisional blocks at the time of cesarean delivery to decrease postoperative pain (Parikh 2019; Prabhu 2018). Use of bupivacaine in obstetrical paracervical block anesthesia is contraindicated (may cause fetal bradycardia and death).Monitoring ParametersCardiovascular and respiratory (adequacy of ventilation) vital signs, state of consciousness, signs of CNS toxicity, pain relief.Mechanism of ActionBlocks both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction.Pharmaco*kinetics (Adult data unless noted)Onset: Rapid (Hu 2013)Duration: Local: Up to 72 hours (Hu 2013); Systemic: Plasma levels can persist for 96 hours after local administration and 120 hours after interscalene brachial plexus nerve block.Absorption: Systemic absorption varies; dependent on dose, route of administration, and vascularity of administration siteProtein binding: 95%Metabolism: Hepatic via conjugation; major metabolite pipecoloxylidine (PPX; inactive)Half-life elimination: 13 to 34 hours (Hu 2013)Time to peak, plasma: Within 1 hour (initial peak); 12 to 36 hours (second peak) (Hu 2013)Excretion: Urine (~6% unchanged)Pharmaco*kinetics: Additional ConsiderationsAltered kidney function: Renal impairment may reduce bupivacaine elimination increasing systemic exposure.Hepatic function impairment: Severe impairment may reduce bupivacaine metabolism increasing systemic exposure.Pricing: USSuspension (Exparel Injection)1.3% (per mL): $23.86Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursem*nt or purchasing functions or considered to be an exact price for a single product and/or manufacturer.Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions.In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data.Pricing data is updated monthly.American College of Obstetricians and Gynecologists' (ACOG) Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 209: Obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. doi:10.1097/AOG.0000000000003132 [PubMed 30801474]Dix SK, Rosner GF, Nayar M, et al, “Intractable Cardiac Arrest Due to Lidocaine Toxicity Successfully Resuscitated With Lipid Emulsion,” Crit Care Med, 2011, 39(4):872-4. [PubMed 21263316]Exparel (bupivacaine liposomal) [prescribing information]. San Diego, CA: Pacira Pharmaceuticals Inc; March 2022.Golf M, Daniels SE, and Onel E, "A Phase 3, Randomized, Placebo-Controlled Trial of Depofoam® Bupivacaine (Extended-Release Bupivacaine Local Analgesic) in Bunionectomy," Adv Ther, 2011, 28(9):776-88. [PubMed 21842428]Gorfine SR, Onel E, Patou G, et al, "Bupivacaine Extended-Release Liposome Injection for Prolonged Postsurgical Analgesia in Patients Undergoing Hemorrhoidectomy: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial," Dis Colon Rectum, 2011, 54(12):1552-9. [PubMed 22067185]Hu D, Onel E, Singla N, Kramer WG, Hadzic A. Pharmaco*kinetic profile of liposome bupivacaine injection following a single administration at the surgical site. Clin Drug Investig. 2013;33(2):109-115. doi: 10.1007/s40261-012-0043-z. [PubMed 23229686]Mustafa HJ, Wong HL, Al-Kofahi M, Schaefer M, Karanam A, Todd MM. Bupivacaine pharmaco*kinetics and breast milk excretion of liposomal bupivacaine administered after cesarean birth. Obstet Gynecol. 2020;136(1):70-76. doi:10.1097/AOG.0000000000003886 [PubMed 32541292]Neal JM, Mulroy MF, and Weinberg GL, “American Society of Regional Anesthesia and Pain Medicine Checklist for Managing Local Anesthetic Systemic Toxicity: 2012 Version,” Reg Anesth Pain Med, 2012, 37(1):16-8. [PubMed 22189574]Parikh P, Sunesara I, Singh Multani S, Patterson B, Lutz E, Martin JN Jr. Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia: a retrospective study. J Matern Fetal Neonatal Med. 2019;32(6):966-970. doi:10.1080/14767058.2017.1397118 [PubMed 29065741]Prabhu M, Clapp MA, McQuaid-Hanson E, et al. Liposomal bupivacaine block at the time of cesarean delivery to decrease postoperative pain: a randomized controlled trial. Obstet Gynecol. 2018;132(1):70-78. doi:10.1097/AOG.0000000000002649 [PubMed 29889750]Topic 131649 Version 15.0

CloseHeat index (Fahrenheit)Heat index (Fahrenheit) Relative humidity (%) Temperature (°F) 80 82 84 86 88 90 92 94 96 98 100 102 104 106 108 110 40 80 81 83 85 88 91 94 97 101 105 109 114 119 124 130 136 45 80 82 84 87 89 93 96 100 104 109 114 119 124 130 137   50 81 83 85 88 91 95 99 103 108 113 118 124 131 137     55 81 84 86 89 93 97 101 106 112 117 124 130 137       60 82 84 88 91 95 100 105 110 116 123 129 137         65 82 85 89 93 98 103 108 114 121 128 136           70 83 86 90 95 100 105 112 119 126 134             75 84 88 92 97 103 109 116 124 132               80 84 89 94 100 106 113 121 129                 85 85 90 96 102 110 117 126 135                 90 86 91 98 105 113 122 131                   95 86 93 100 108 117 127                     100 87 95 103 112 121 132                       Likelihood of heat disorders with prolonged exposure or strenuous activity   Caution   Extreme caution   Danger   Extreme danger  Data from: Heat Forecast Tools. National Weather Service. Available at: https://www.weather.gov/safety/heat-index (Accessed on August 25, 2021).Graphic 133126 Version 1.0