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Variability in Aminoglycoside Pharmacokinetics in Critically III Surgical Patients
PERIOPERATIVE CARE
221
standard §u:rgical §c:rub§. This report coilaborates the findings of previous investigators who have used this foam 1 • 2 and it would appear that this technique merits further evaluation by urofogists. Charles B. Brendle:r, M.D.
maintenance doses and, after necessary dosage adjustments, samples should be obtained in the same manner every 2 to 4 d.ays depending on the clinical status and renal function. Charles B. Brendlel1', M,D.
L Gravens, D. L., Butcher, H. R., Jr., Ballinger, W. F. and Dewm·, M. E.: Septisol antiseptic foam for hands of operating room personnel: an effective antibacterial agent. Surgery, 73: 360, 1973. 2. Eitzen, H. E., Ritter, M.A., French, M. L. V. and Gioe, T. J.: A microbiological in-use comparison of surgical handwashing agents. J. Bone Joi.nt Surg., 61A: 403, 1979.
Preoperative Parenteral Nutrition in the High Risk Surgical Patient
Variability in Aminoglycoside Pharmacokinetics in Critically m Surgical Patients J. F, DASTA AND D. K. ARMSTRONG, Division of Pharmacy Practice and Department of Anesthesiology, The Ohio State University, Colleges of Pharmacy and Medicine, Columbus, Ohio
Crit. Care Med., 16: 327-330, 1988 The pharmacokinetics of the aminoglycosides were evaluated in 181 patients admitted to a surgical ICU. Pharmacokinetic parameters changed from 16% to 40% during therapy requiring multiple dosage adjustments and nearly nine drug levels per patient. Dosage adjustments resulted in peak and trough serum concentrations within the therapeutic range 71 % and 74 % of the time, Aminoglycoside half-life (T½) ranged from 1.1 to 69.3 h. Aminoglycoside volume of distribution also varied considerably with an average value of 0.36 L/kg, During therapy most patients gained weight (average 8.4 kg) which correlated with their corresponding fluid gain of 11.6 L. Pharmacokinetic parameters were variable even in patients with a normal serum creatinine. Less than 50% of these patients received the recommended daily dosages, This study suggests that the aminoglycoside volume of distribution in critically ill surgical patients differs from general hospital patients and pharmacokinetic parameters change considerably during therapy. We recommend obtaining timed serum aminoglycoside concentrations early in therapy and adjusting drug dosages as needed to maintain serum concentrations in the therapeutic range. Editorial Comment: Aminoglycosides are used commonly to t:reat gram-negative infectiorrn frequently arising in. the urinary tract. Because of their nanow therapeutic 1·an.ge serum concentrations of aminoglycosides mm,t be monitored closely to minimize toxicity, This is true especially in critically m patients who may u.nde:rgo significant hemodynamic ciumges du.iring therapy, This study characterizes changes in the pharmacokinetics of aminoglycosides during treatment of surgical intensive care patients. The authors fmrn.d that pha:rmacokinetic parameters changed an average of 26 per cent during therapy requiring multiple dosage adjustments in nearly all patients, the aminoglycoside half-life :ranged from 1.1 to 67.3 hours, 24 per cent of renal failure patients never achieved a consistent dosage because of continuously changing pharmacokinetic parameters and pharmacokinetic parameters were variable even in patients with a normal serum creatinine with variation in aminoglycoside half-life from 1.2 to 17 .8 hours. The authors recommend that serum concentrations of aminoglycosides be measured 1 hour after completion of the first infusion and at 1.5 to 2 times the elimination half-life. Measurements should be repeated after the first few
R.
BELLANTONE, G. B. DOGLIETTO, M. BOSSOLA, F. PACELLI, F. NEGRO, L. SOFO AND F. CRUCITTI, Universita
Cattolica del Sacra Cuore, Istituto di Semeiotica Chirurgica, Rome, Italy J, Parent. Ent. Nutr., 12: 195-197, 1988
In order to assess the significance of malnutrition in determining surgical complications and the possibility of their reduction by preoperative nutritional support (PNS), a randomized controlled trial is being performed at our institution. The results relative to 100 patients who underwent major surgery for gastrointestinal disease, are presented here. In the treatment group 49 patients received 30 kcal/kg/day and 200 mg/kg/day of nitrogen for at least 7 days in the immediate preoperative period (nine patients were excluded from this group due to early surgery-seven cases; or refusal to accept PNS-two cases. Data analysis with their inclusion or exclusion showed similar results.) Fifty-one patients constituted the control group. The observed septic complication rate was, respectively, 30 and 35.3% (p:NS). When the analysis was restricted to the patients with abnormal instant nutritional assessment (INA), as defined by Seltzer et al (serum albumin <3.5 g/dl and/or total lymphocyte count <1500 cells/mm3 ), a statistically significant difference was observed in the incidence of sepsis between the two subgroups (21 % us 53.3%, p <0.05). Analogous results were obtained from the patients who underwent gastrectomy for gastric cancer: 16. 7% of septic complications in the malnourished treated patients and 100% in the malnourished control ones (p <0.05), The occurrence of serious sepsis (sepsis score ::::: 10, according to the scoring system developed by Elebute and Stoner) in the malnourished subgroups was 5.2% and 26.7%, respectively, (p = 0.09). The postoperative mortality rate was not significantly changed by the PNS (reduction from 3.9% to 2.5%, p:NS), This result was expected since power analysis indicates a too large number of patients would be needed to show a statistically significant difference in this low mortality risk category of patients. Our study suggests that malnourished patients waiting for major gastrointestinal surgery may benefit from an adequate PNS that seems to significantly reduce septic complication rate. Editorial Comment: Malnutrition is associated with increased postoperative morbidity and mortality in surgical patients. The authors studied the effectiveness of preoperative nutritional support on reducing postoperative septic complications (wound infection, pneumonia, intra-abdominal infection and septicemia) in high risk gastrointestinal surgical patients. Preoperative nutritional support was administered as a supplement to the oral diet for at least 7 days, providing 30 kcal./kg. per day and 200 mg./kg. per day of nitrogen. Over-all, there was no significant difference in the rate of septic complications between patients receiving preoperative nu-
221
standard §u:rgical §c:rub§. This report coilaborates the findings of previous investigators who have used this foam 1 • 2 and it would appear that this technique merits further evaluation by urofogists. Charles B. Brendle:r, M.D.
maintenance doses and, after necessary dosage adjustments, samples should be obtained in the same manner every 2 to 4 d.ays depending on the clinical status and renal function. Charles B. Brendlel1', M,D.
L Gravens, D. L., Butcher, H. R., Jr., Ballinger, W. F. and Dewm·, M. E.: Septisol antiseptic foam for hands of operating room personnel: an effective antibacterial agent. Surgery, 73: 360, 1973. 2. Eitzen, H. E., Ritter, M.A., French, M. L. V. and Gioe, T. J.: A microbiological in-use comparison of surgical handwashing agents. J. Bone Joi.nt Surg., 61A: 403, 1979.
Preoperative Parenteral Nutrition in the High Risk Surgical Patient
Variability in Aminoglycoside Pharmacokinetics in Critically m Surgical Patients J. F, DASTA AND D. K. ARMSTRONG, Division of Pharmacy Practice and Department of Anesthesiology, The Ohio State University, Colleges of Pharmacy and Medicine, Columbus, Ohio
Crit. Care Med., 16: 327-330, 1988 The pharmacokinetics of the aminoglycosides were evaluated in 181 patients admitted to a surgical ICU. Pharmacokinetic parameters changed from 16% to 40% during therapy requiring multiple dosage adjustments and nearly nine drug levels per patient. Dosage adjustments resulted in peak and trough serum concentrations within the therapeutic range 71 % and 74 % of the time, Aminoglycoside half-life (T½) ranged from 1.1 to 69.3 h. Aminoglycoside volume of distribution also varied considerably with an average value of 0.36 L/kg, During therapy most patients gained weight (average 8.4 kg) which correlated with their corresponding fluid gain of 11.6 L. Pharmacokinetic parameters were variable even in patients with a normal serum creatinine. Less than 50% of these patients received the recommended daily dosages, This study suggests that the aminoglycoside volume of distribution in critically ill surgical patients differs from general hospital patients and pharmacokinetic parameters change considerably during therapy. We recommend obtaining timed serum aminoglycoside concentrations early in therapy and adjusting drug dosages as needed to maintain serum concentrations in the therapeutic range. Editorial Comment: Aminoglycosides are used commonly to t:reat gram-negative infectiorrn frequently arising in. the urinary tract. Because of their nanow therapeutic 1·an.ge serum concentrations of aminoglycosides mm,t be monitored closely to minimize toxicity, This is true especially in critically m patients who may u.nde:rgo significant hemodynamic ciumges du.iring therapy, This study characterizes changes in the pharmacokinetics of aminoglycosides during treatment of surgical intensive care patients. The authors fmrn.d that pha:rmacokinetic parameters changed an average of 26 per cent during therapy requiring multiple dosage adjustments in nearly all patients, the aminoglycoside half-life :ranged from 1.1 to 67.3 hours, 24 per cent of renal failure patients never achieved a consistent dosage because of continuously changing pharmacokinetic parameters and pharmacokinetic parameters were variable even in patients with a normal serum creatinine with variation in aminoglycoside half-life from 1.2 to 17 .8 hours. The authors recommend that serum concentrations of aminoglycosides be measured 1 hour after completion of the first infusion and at 1.5 to 2 times the elimination half-life. Measurements should be repeated after the first few
R.
BELLANTONE, G. B. DOGLIETTO, M. BOSSOLA, F. PACELLI, F. NEGRO, L. SOFO AND F. CRUCITTI, Universita
Cattolica del Sacra Cuore, Istituto di Semeiotica Chirurgica, Rome, Italy J, Parent. Ent. Nutr., 12: 195-197, 1988
In order to assess the significance of malnutrition in determining surgical complications and the possibility of their reduction by preoperative nutritional support (PNS), a randomized controlled trial is being performed at our institution. The results relative to 100 patients who underwent major surgery for gastrointestinal disease, are presented here. In the treatment group 49 patients received 30 kcal/kg/day and 200 mg/kg/day of nitrogen for at least 7 days in the immediate preoperative period (nine patients were excluded from this group due to early surgery-seven cases; or refusal to accept PNS-two cases. Data analysis with their inclusion or exclusion showed similar results.) Fifty-one patients constituted the control group. The observed septic complication rate was, respectively, 30 and 35.3% (p:NS). When the analysis was restricted to the patients with abnormal instant nutritional assessment (INA), as defined by Seltzer et al (serum albumin <3.5 g/dl and/or total lymphocyte count <1500 cells/mm3 ), a statistically significant difference was observed in the incidence of sepsis between the two subgroups (21 % us 53.3%, p <0.05). Analogous results were obtained from the patients who underwent gastrectomy for gastric cancer: 16. 7% of septic complications in the malnourished treated patients and 100% in the malnourished control ones (p <0.05), The occurrence of serious sepsis (sepsis score ::::: 10, according to the scoring system developed by Elebute and Stoner) in the malnourished subgroups was 5.2% and 26.7%, respectively, (p = 0.09). The postoperative mortality rate was not significantly changed by the PNS (reduction from 3.9% to 2.5%, p:NS), This result was expected since power analysis indicates a too large number of patients would be needed to show a statistically significant difference in this low mortality risk category of patients. Our study suggests that malnourished patients waiting for major gastrointestinal surgery may benefit from an adequate PNS that seems to significantly reduce septic complication rate. Editorial Comment: Malnutrition is associated with increased postoperative morbidity and mortality in surgical patients. The authors studied the effectiveness of preoperative nutritional support on reducing postoperative septic complications (wound infection, pneumonia, intra-abdominal infection and septicemia) in high risk gastrointestinal surgical patients. Preoperative nutritional support was administered as a supplement to the oral diet for at least 7 days, providing 30 kcal./kg. per day and 200 mg./kg. per day of nitrogen. Over-all, there was no significant difference in the rate of septic complications between patients receiving preoperative nu-