Gentamicin pharmacokinetics during slow daily home hemodialysis

BACKGROUND: Gentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmacokinetics for SDH hemodialysis patients. METHODS: Eight patients (four male and four female) received a single intravenous dose of 0.6 mg/kg gentamicin post-hemodialysis. Blood samples were collected at 5, 10, 15, 30, and 60 minutes after dose. The next day patients underwent a typical SDH hemodialysis (high-flux F50NR dialyzer) session. Blood samples were taken at 0, 5, 15, 60, 120, 240, 360, 480 minutes during and 15, 30 and 60 minutes post-hemodialysis. Baseline and 24-hour urine samples were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. RESULTS: Patients were 42.5 +/- 13.1 years old (mean +/- SD). Inter-, intra-, and post-hemodialysis collection periods were 17.0 +/- 2.1 hours, 8.1 +/- 0.4 hours, and 1.1 +/- 0.1 hours, respectively. Intra-, and interdialytic gentamicin half-lives were different (intradialytic, 3.7 +/- 0.8 hours; interdialytic, 20.4 +/- 4.7 hours; P < 0.0001). Hemodialysis clearance accounted for 70.5% gentamicin total clearance. Renal clearance correlated with glomerular filtration rate (GFR) (renal clearance=1.2 GFR; r2=0.98; P < 0.001). Mean peak and trough of hemodialysis concentrations were 1.8 +/- 0.6 microg/mL and 0.5 +/- 0.2 microg/mL, respectively. Post-hemodialysis rebound was 3.1 +/- 8.8% at 1 hour. CONCLUSION: Pharmacokinetic model predicts 2.0 to 2.5 mg/kg dose gentamicin post-hemodialysis would provide peak (1 hour post-dose) and trough (end of SDH hemodialysis session) concentrations of 6.0 to 7.5 microg/mL and 0.7 to 0.8 microg/mL, respectively. This would provide adequate coverage for most gram-negative organisms in SDH hemodialysis patients.     

The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting.

Acute deterioration in ventricular function and oxygen transport is common after cardiac surgery. We hypothesized that milrinone or amrinone may reduce their occurrence and catecholamine requirements and increase cellular enzyme levels in patients undergoing coronary artery bypass. In 45 patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg x kg(-1) x min(-1) infusion for 10 h, amrinone 1.5 mg/kg plus 10 microg x kg(-1) x min(-1) infusion for 10 h, or placebo at release of aortic cross-clamp. Hemodynamic variables, dopamine requirement, and laboratory values were recorded. At the postoperative nadir, stroke volume index was higher in the Milrinone and Amrinone groups (mean +/- SD, 27.8 +/- 4.0 and 26.1 +/- 3.2 vs. 20.4 +/- 5.1 mL x min (-1) x m(-2) per beat, P < 0.0001), and oxygen transport index was higher (354.7 +/- 57.8 and 353.7 +/- 91.2 vs 283.0 +/- 83.9 mL. min(-1) x m(-2), P = 0.009). The postoperative dopamine requirement was less (6.6 +/- 2.7 and 6.8 +/- 2.6 vs 10.4 +/- 2.0 mg/kg, P < 0.008), and postoperative serum lactate, alanine and aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, C-reactive protein, and glucose levels were less (P < 0.01). The mean postoperative heart rate was faster in the Milrinone group than in the Amrinone and Placebo groups (96.8 +/- 10.3 vs. 86.9 +/- 9.5 and 87.8 +/- 10.8 bpm, P < 0.01). Milrinone and amrinone administered preemptively reduce postoperative deterioration in cardiac function and oxygen transport, dopamine requirement, and increases in serum lactate, glucose, and enzyme levels, although milrinone may increase heart rate. IMPLICATIONS: Preemptive milrinone or amrinone administration before separation from cardiopulmonary bypass in cardiac surgical patients not only ameliorates postoperative deterioration in cardiac function and oxygen transport, but also reduces dopamine requirement and increases serum lactate, glucose, and cellular enzyme levels, although milrinone may increase heart rate.     

Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study

OBJECTIVE: The purpose of this study was to evaluate the renoprotective effects of fenoldopam in patients at high risk of postoperative acute kidney injury undergoing elective cardiac surgery requiring cardiopulmonary bypass. DESIGN: A double-blind randomized clinical trial. Setting: Hospital. Participants: One hundred ninety-three patients. Interventions: Patients undergoing cardiac surgery were randomly assigned to receive a continuous infusion of fenoldopam, 0.1 microg/kg/min (95 patients), or placebo (98 patients) for 24 hours. Patients were included if at least 1 of the following risk factors was present: preoperative serum creatinine > or =1.5 mg/dL, age >70 years, diabetes mellitus, or prior cardiac surgery. Serum creatinine and urinary output were measured at baseline (T1), 24 hours (T2), and 48 hours after surgery (T3). Acute kidney injury was defined as a postoperative serum creatinine level of > or =2 mg/dL with an increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to maximum postoperative values. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury developed in 12 of 95 (12.6%) patients receiving fenoldopam and in 27 of 98 (27.6%) patients receiving placebo (p = 0.02), whereas renal replacement therapy was started in 0 of 95 and 8 of 98 (8.2%) patients, respectively (p = 0.004). Serum creatinine was similar at baseline (1.8 +/- 0.4 mg/dL v 1.9 +/- 0.3 mg/dL) in the fenoldopam and placebo groups but differed significantly (p < 0.001 and p < 0.001) 24 hours (1.6 +/- 0.2 mg/dL v 2.5 +/- 0.6 mg/dL) and 48 hours (1.5 +/- 0.3 mg/dL v 2.8 +/- 0.4 mg/dL) after the operation. CONCLUSIONS: A 24-hour infusion of 0.1 mug/kg/min of fenoldopam prevented acute kidney injury in a high-risk population undergoing cardiac surgery.     

Evaluation of efficacy and plasma concentrations of ropivacaine in continuous axillary brachial plexus block: high dose for surgical anesthesia and low dose for postoperative analgesia

BACKGROUND AND OBJECTIVES: Ropivacaine is a potent local anesthetic that, experimentally at low concentrations, produces an effective block of pain conducting nerve fibers. Therefore, it was hypothesized that 0.1% and 0.2% ropivacaine would provide clinically adequate postoperative analgesia in continuous axillary plexus block. METHODS: Sixty patients (ASA I-II) scheduled for elective hand or forearm surgery received 5 mg/kg of 0.75% ropivacaine for axillary block using nerve stimulator technique. One hour later, in random order, a continuous infusion of either 0.1% ropivacaine (0.125 mg/kg/h), 0.2% ropivacaine (0.25 mg/kg/h) or saline 6 to 11 mL/h was started. RESULTS: The mean total ropivacaine dose for the surgical block was 5.1 to 5.2 mg/kg with the supplementation. All patients were pain free for the first 12 to 15 hours after the block. The need for postoperative analgesics during the infusion was similar in all groups. After the initial block, the maximum plasma concentrations (mean 2.5 microg/mL) were measured at 45 or 60 minutes after injection. The highest individual plasma concentration was 4.2 microg/mL. Despite the high venous peak concentration, no toxic reactions were observed. The mean peak plasma concentration (Cmax) was 2.2+/-0.5 microg/mL for saline, 2.6+/-0.8 microg/mL for 0.1% ropivacaine, and 2.6+/-0.7 microg/mL for 0.2% ropivacaine. During the continuous infusion of 24 hours, the ropivacaine concentration declined steadily. CONCLUSIONS: Ropivacaine is safe and effective for axillary brachial plexus block. The continuous infusion of 0.1% or 0.2% ropivacaine was no more beneficial than an infusion of saline in relieving postoperative pain in patients having elective hand surgery. None of the infusions were sufficient to adequately treat the patients' pain without the addition of adjunct agents.     

Cardiovascular effect of 7.5% sodium chloride-dextran infusion after thermal injury.

HYPOTHESIS: Clinical study can help determine the safety and cardiovascular and systemic effects of an early infusion of 7.5% sodium chloride in 6% dextran-70 (hypertonic saline-dextran-70 [HSD]) given as an adjuvant to a standard resuscitation with lactated Ringer (RL) solution following severe thermal injury. DESIGN: Prospective clinical study. SETTING: Intensive care unit of tertiary referral burn care center. PATIENTS: Eighteen patients with thermal injury over more than 35% of the total body surface area (TBSA) (range, 36%-71%) were studied. INTERVENTIONS: Eight patients (mean +/- SEM, 48.2% +/- 2% TBSA) received a 4-mL/kg HSD infusion approximately 3.5 hours (range, 1.5-5.0 hours) after thermal injury in addition to routine RL resuscitation. Ten patients (46.0% +/- 6% TBSA) received RL resuscitation alone. MAIN OUTCOME MEASURES: Pulmonary artery catheters were employed to monitor cardiac function, while hemodynamic, metabolic, and biochemical measurements were taken for 24 hours. RESULTS: Serum troponin I levels, while detectable in all patients, were significantly lower after HSD compared with RL alone (mean +/- SEM, 0.45 +/- 0.32 vs 1.35 +/- 0.35 microg/L at 8 hours, 0.88 +/- 0.55 vs 2.21 +/- 0.35 microg/L at 12 hours). While cardiac output increased proportionately between 4 and 24 hours in both groups (from 5.79 +/- 0.8 to 9.45 +/- 1.1 L/min [mean +/- SEM] for HSD vs from 5.4 +/- 0.4 to 9.46 +/- 1.22 L/min for RL), filling pressure (central venous pressure and pulmonary capillary wedge pressure) remained low for 12 hours after HSD infusion (P = .048). Total fluid requirements at 8 hours (2.76 +/- 0.7 mL/kg per each 1% TBSA burned [mean +/- SEM] for HSD vs 2.67 +/- 0.24 mL/kg per each 1% TBSA burned for RL) and 24 hours (6.11 +/- 4.4 vs 6.76 +/- 0.75 mL/kg per each 1% TBSA burned) were similar. Blood pressure remained unchanged, and serum sodium levels did not exceed 150 +/- 2 mmol/L (mean +/- SD) in either group. CONCLUSIONS: The absence of deleterious hemodynamic or metabolic side effects following HSD infusion in patients with major thermal injury confirms the safety of this resuscitation strategy. Postburn cardiac dysfunction was demonstrated in all burn patients through the use of cardiospecific serum markers and pulmonary artery catheter monitoring. Early administration of HSD after a severe thermal injury may reduce burn-related cardiac dysfunction, but it had no effect on the volume of resuscitation or serum biochemistry values.     

Continuous infusion of remifentanil and target-controlled infusion of propofol for patients undergoing cardiac surgery: a new approach for scheduled early extubation

OBJECTIVE: To assess hemodynamic stability, postoperative pain management, and the control and timing of early extubation of a total intravenous anesthetic technique using propofol target-controlled infusion (TCI) and remifentanil in cardiac surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Fifty patients scheduled for elective cardiac surgery. INTERVENTIONS: Premedication consisted of oral midazolam, 0.1 mg/kg. Anesthesia was induced with propofol TCI at a target concentration of 1.5 to 2 microg/mL; remifentanil, 1 microg/kg; and rocuronium. Anesthesia was maintained with propofol at the same target concentration and remifentanil titrated between 0.25 and 1 microg/kg/min. Thirty minutes before the end of surgery, a 0.1-mg/kg bolus of morphine was administered intravenously. Postoperative sedation was achieved by maintaining the propofol infusion until the patient was deemed ready for extubation. Postoperative pain relief was evaluated using a visual analog scale. The intervals between arrival in the intensive care unit, spontaneous ventilation, and extubation were recorded. MEASUREMENTS AND MAIN RESULTS: Included in this study were 36 men and 14 women (American Society of Anesthesiologist = III; New York Heart Association = II) scheduled for cardiac surgery. All patients remained hemodynamically stable throughout the perioperative period. Thirty-seven patients were successfully extubated during the first 4 postoperative hours. Spontaneous breathing was achieved at a mean interval of 15+/-5 minutes after propofol discontinuation. The mean interval to extubation was 163+/-45 minutes after arrival in the intensive care unit. Extubation was performed 48+/-12 minutes after patients were considered ready to awaken. During spontaneous ventilation, 36 patients received additional boluses of morphine (mean, 2.5+/-1 mg). Subsequently, all patients achieved a visual analog scale less than 40 mm. CONCLUSION: The combination of remifentanil and propofol TCI resulted in hemodynamic stability and good postoperative analgesia. This technique allows physicians to schedule the time of extubation in patients undergoing cardiac anesthesia.     

Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.     

Usefulness of tranexamic acid in cranial remodeling surgery

OBJECTIVES: To assess the usefulness of tranexamic acid (TA) in pediatric cranial remodeling surgery, by analyzing its effects on bleeding and transfusion requirements, number of days of cranial drainage required, and time spent in the postoperative recovery unit. MATERIAL AND METHOD: A single-blind, controlled study was designed with 20 patients (10 cases and 10 controls) randomly assigned to receive or not receive 15 mg/kg of intravenous TA upon anesthetic induction, every 4 hours during surgery, and every 8 hours throughout the 48 hours after surgery. Variables analyzed were results of blood tests, blood loss, volume transfused, time in the recovery unit, and complications related to TA infusion. RESULTS: The group treated with TA experienced less bleeding during surgery than did the controls (199 +/- 60 vs 290 +/- 43 mL) and had less need of intraoperative (176 +/- 104 vs 206 +/- 70 mL) and postoperative transfusion (9 +/- 28 vs 52 +/- 72 mL) 24 hours after surgery. TA group patients also spent less time in the recovery unit (60 +/- 14 vs 72 +/- 11 hours). Blood test variables in TA-treated children were also better 24 hours after surgery with regard to hemoglobin (12.1 +/- 2 vs 11.6 +/- 1.3 mg/dL) and platelet (261 +/- 68.5 vs 181.6 +/- 58.1 platelets/mm3) concentrations, and cephalin time (33 +/- 12 vs 49 +/- 16 seconds). No complications related to TA treatment were observed. CONCLUSIONS: TA can reduce perioperative bleeding in the context of pediatric cranial remodeling surgery. TA-treated patients have less need of transfusion and this may reduce the rate of related complications as well a make care more efficient.     

The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery

We investigated the effect of lidocaine on the incidence of cognitive dysfunction in the early postoperative period after cardiac surgery. One-hundred-eighteen patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB) were randomized to receive either lidocaine (1.5 mg/kg bolus followed by a 4 mg/min infusion during operation and 4 mg/kg in the priming solution of CPB) or placebo. A battery of nine neuropsychological tests was administered before and 9 days after surgery. A postoperative deficit in any test was defined as a decline by more than or equal to the preoperative SD of that test in all patients. Any patient showing a deficit in two or more tests was defined as having postoperative cognitive dysfunction. Eighty-eight patients completed pre- and postoperative neuropsychological tests. Plasma lidocaine concentrations (microg/mL) were 4.78 +/- 0.52 (mean +/- SD), 5.38 +/- 0.95, 4.52 +/- 0.39, 5.82 +/- 0.76, and 7.10 +/- 1.09 at 10 min before CPB; 10, 30, and 60 min of CPB; and at the end of operation, respectively. The proportion of patients showing postoperative cognitive dysfunction was significantly reduced in the lidocaine group compared with that in the placebo group (18.6% versus 40.0%; P = 0.028). We conclude that intraoperative administration of lidocaine decreased the occurrence of cognitive dysfunction in the early postoperative period. IMPLICATIONS: Postoperative cognitive dysfunction is a commonly recognized complication after cardiac surgery. Intraoperative cerebral microembolism and hypoperfusion have been proposed to be the major mechanisms. The results of this study show that intraoperative administration of lidocaine decreased the occurrence of early postoperative cognitive dysfunction, perhaps because of its neuroprotective effects.     

Cefazolin versus cefamandole for prophylaxis during total joint arthroplasty

A prospective, randomized, double-blind comparison of cefazolin versus cefamandole was carried out to evaluate safety and efficacy and to determine bone and serum antibiotic concentrations in patients undergoing total joint arthroplasty. Dosages were 1 g of cefazolin before surgery followed by 500 mg every eight hours for six doses, versus 2 g of cefamandole before surgery followed by 1 g every eight hours for six doses. Intraoperative doses were given during prolonged procedures. No significant adverse drug reactions were clearly attributable to either drug. Among 48 patients receiving cefazolin there was one postoperative wound infection and one distant site infection. Among 49 patients receiving cefamandole, there were two postoperative wound infections and two distant site infections. No deep wound infections occurred in either group during at least 48 months of follow-up study. In hip specimens removed at surgery, the mean antibiotic concentrations were 1.6 +/- 1.4 micrograms/g for cefazolin recipients, compared with 5.7 +/- 5.9 micrograms/g for cefamandole recipients (p less than .001). In knee specimens, the mean antibiotic concentrations were 0.64 +/- 0.57 microgram/g for cefazolin recipients compared to 3.8 +/- 3.4 micrograms/g for cefamandole recipients (p = .004). Cefazolin given at one-half the dose of cefamandole appeared to be equally safe and effective but resulted in lower bone concentrations of antibiotic.     

Fast-track cardiac anesthesia: a comparison of remifentanil plus intrathecal morphine with sufentanil in a desflurane-based anesthetic

OBJECTIVE: To compare the effects of an intravenous remifentanil infusion plus intrathecal morphine with intravenous sufentanil infusion with respect to intraoperative hemodynamic variables, extubation times, and recovery profiles when administered as part of a desflurane-based fast-track anesthetic regimen for cardiac surgery. DESIGN: A prospective, randomized, nonblinded study. SETTING: University hospital. PARTICIPANTS: Forty patients undergoing elective primary coronary artery bypass graft, aortic valve replacement, or mitral valve replacement surgery. INTERVENTIONS: After a standardized anesthetic induction, anesthesia was maintained with a remifentanil infusion, 0.1 microg/kg/min, and desflurane, 3% to 10%, inspired (group I, n = 20) or a sufentanil infusion, 0.3 microg/kg/h, and desflurane, 3% to 10%, inspired (group II, n = 20). Patients receiving remifentanil were administered intrathecal morphine, 8 microg/ kg, for postoperative analgesia. MEASUREMENTS AND MAIN RESULTS: Both anesthetic regimens provided comparable intraoperative hemodynamic stability and similar recovery profiles, with extubation times of 5.1 +/- 4.3 hours (group I) and 5.8 +/- 6.7 hours (group II). CONCLUSIONS: Use of remifentanil in combination with intrathecal morphine did not facilitate earlier tracheal extubation or improve intraoperative hemodynamic stability compared with sufentanil alone for fast-track cardiac anesthesia.     

Hypophosphatemia following open heart surgery: incidence and consequences.

OBJECTIVE: Significant hypophosphatemia (SH) is common after major surgery and may be associated with considerable morbidity, including respiratory and cardiac failure. The contribution of SH to these complications after cardiac surgery is not well defined. METHODS: In this prospective study, levels of serum phosphorus and other electrolytes (potassium, magnesium and calcium) were measured in 566 consecutive patients (395 men, 182 women; mean age 65.5+/-11.1 years) undergoing elective cardiac surgery at three time points: prior to surgery, immediately on admission to the ICU, and on the first postoperative day. Preoperative (type of surgery, Bernstein-Parsonnet risk estimate), intraoperative (duration of bypass and cross-clamp, intraoperative fluid and blood product use) and postoperative data (duration of ventilation, duration of ICU and hospital stay, requirement for cardioactive drug support, development of atrial fibrillation, and mortality) were collected. Patients were divided into two groups according to the immediate postoperative phosphate level: SH, phosphate <0.48 mmol/l (mean phosphate 0.28+/-0.13 mmol/l, n = 194), and a control group (mean phosphate value 0.84+/-0.08 mmol/l, n = 372). Patients with SH received treatment with sodium or potassium phosphate (0.8 mmol/kg body weight over 6-12 h). RESULTS: SH was present in 34.3% of patients. There were no differences in the baseline characteristics between the two groups. Patients with SH received more intraoperative blood product transfusions. The postoperative course of patients with SH was characterized by prolonged ventilation (2.1+/-1.7 versus 1.1+/-0.9 days, P = 0.05), more patients requiring cardioactive drugs (12-24 h 16 versus 10.9%, P = 0.05 and >24 h 23.5 versus 13.8%, P = 0.05); and a prolonged hospital stay (7.8+/-3.4 versus 5.6+/-2.5 days, P = 0.05). CONCLUSIONS: SH was common after open-heart surgery and was associated with an increased incidence of important complications. We suggest that phosphate levels be routinely measured immediately after surgery and appropriate therapy instituted.     

Intraoperative glucose control in diabetic and nondiabetic patients during cardiac surgery

OBJECTIVE: The purpose of this study was to evaluate intraoperative glucose control. DESIGN: Prospective unblinded study. SETTING: Tertiary care center. PARTICIPANTS: Diabetic (n = 17) and nondiabetic (n = 23) patients undergoing elective cardiac surgery. INTERVENTIONS: Diabetics received a modified insulin regimen consisting of a fixed rate infusion of regular insulin, 10 U/m2/h, and a variable infusion of D10W, adjusted to maintain glucose between 101 to 140 mg/dL. MEASUREMENTS AND MAIN RESULTS: Baseline glucose was higher in diabetics versus nondiabetics (mean +/- standard error of the mean: 203 +/- 27 v 117 +/- 3 mg/dL, p < 0.005). After baseline, insulin levels were increased in diabetics to 410 to 568 microU/mL. Corresponding insulin levels in nondiabetics were 12 to 40 microU/mL. Compared with baseline, glucose was decreased by 10% +/- 29% in diabetics during hypothermic cardiopulmonary bypass and increased by 21% +/- 30% in nondiabetics (p < 0.005). After discontinuation of bypass, glucose was lower in diabetics (137 +/- 12 mg/dL) versus nondiabetics (162 +/- 8 mg/dL, p < 0.005). Nine diabetics had adequate intraoperative glycemic control during hypothermic bypass (glucose 123 +/- 8 mg/dL, insulin 550 +/- 68 microU/mL, glucose infusion rate 1.87 +/- 0.29 mg/kg/min), 6 approached adequate control near the end of surgery (glucose 147 +/- 8 mg/dL, insulin 483 +/- 86 microU/mL, glucose infusion rate 0.35 +/- 0.05 mg/kg/min), and 2 never achieved control. Diabetics with elevated initial glucose >300 mg/dL did not achieve adequate glycemic control. Four diabetics (3 with renal failure) required injection of 50% dextrose after bypass for hypoglycemia. CONCLUSION: Adequate glycemic control can be achieved in most diabetics during cardiac surgery using a modified insulin clamp technique provided initial glucose is <300 mg/dL.     

Plasma concentrations of fluconazole after a single oral dose and administration in drinking water in cockatiels (Nymphicus hollandicus)

Candidiasis frequently affects the oropharynx, esophagus, and crop of juvenile birds with immature immune systems and adult birds that have received long-term antibiotic treatment. Fluconazole is used extensively in human medicine to treat mucosal and invasive candidiasis and has been used in birds; however, there have been few pharmacokinetic studies in avian species to guide safe and effective treatment. The purpose of the present study was to investigate the disposition of fluconazole in cockatiels (Nymphicus hollandicus) after single oral dose administration and to determine if therapeutic plasma concentrations could be safely achieved by providing medicated water. Twenty-eight cockatiels were placed into 7 groups and were orally administered a 10 mg/kg fluconazole suspension. Blood samples were collected from each group for plasma fluconazole assay at serial time points. Fluconazole-medicated drinking water was prepared daily and offered to 15 cockatiels at a concentration of 100 mg/L for 8 days. Blood was collected for plasma fluconazole assay at 2 time points on days 3 and 7. When using naive averaged data in the single-dose study, pharmacokinetic parameters were similar for both compartmental and noncompartmental analyses. The elimination half-life of fluconazole was 19.01 hours, maximum plasma concentration was 4.94 microg/mL, time until maximal concentration was 3.42 hours, and the area under the plasma concentration versus time curve (AUC) was 149.28 h x microg/mL. Computer-simulated trough and peak plasma concentrations at steady-state after multiple doses of fluconazole at 10 mg/kg every 24 hours, 10 mg/kg every 48 hours, and 5 mg/kg every 24 hours were approximately 4.1-8.5 microg/mL, 1.2-6.0 microg/mL, and 2.0-4.3 microg/mL, respectively. Mean +/- SD plasma fluconazole concentrations for the 100 mg/L medicated water study at 0800 and 1600 hours on day 3 were 3.69 +/- 1.22 microg/mL (range, 1.73-5.26 microg/mL) and 4.17 +/- 1.96 microg/mL (range, 3.58-7.49 microg/mL), respectively, and at 0800 and 1600 hours on day 7 were 4.78 +/- 0.91 microg/mL (range, 2.62-6.11 microg/mL) and 6.61 +/- 1.67 microg/mL (range, 3.76-8.78 microg/ mL), respectively. Treatment with fluconazole administered orally at a dosage of 5 mg/kg once daily or 10 mg/kg every 48 hours or fluconazole administered in the drinking water at a concentration of 100 mg/L is predicted to maintain plasma concentrations in most cockatiels that exceed the minimum inhibitory concentration of 90% or therapeutic AUC:MIC of most strains of Candida albicans (by using susceptibility data from humans). The compounded oral suspension was stable for 14 days when stored at 5 degrees C (41 degree sF) and protected from light.     

Serum levels of prophylactic cefazolin during cardiopulmonary bypass surgery

BACKGROUND: Controversy exists regarding the appropriate prophylactic dose of cefazolin for coronary artery bypass grafting (CABG) surgery requiring cardiopulmonary bypass (CPB) because the effect of CPB on serum drug levels is poorly understood. Current standards of prophylaxis are based primarily on empiric studies. Few studies have attempted to quantify serum cefazolin levels in either cardiac or noncardiac surgeries. This study was conducted to measure and assess the adequacy of the intraoperative serum levels of prophylactic cefazolin in CPB surgery. METHODS: This prospective study serially measured six intraoperative serum cefazolin levels in 10 subjects undergoing elective and urgent CABG surgery. We compared the serum levels with the minimum inhibitory concentrations (MIC90) for the most common organisms causing postoperative infection. RESULTS: Serum-free cefazolin levels fluctuated considerably during the operation but remained above the MIC90, for Staphylococcus aureus and S. epidermidis. The serum levels fell below the MIC90 for Enterobacter, Serratia, Escherichia coli, and Proteus mirabilis. CONCLUSIONS: Serum cefazolin levels during CPB remained consistently above the MIC for two of the three main organisms causing postoperative infection but were suboptimal for the remainder. Additional studies are needed to assess the intraoperative serum levels of single-dose cefazolin prophylaxis and to explore alternate dosing methods that minimize intraoperative fluctuations in serum cefazolin levels.     

Normalization of intraoperative parathyroid hormone does not predict normal postoperative parathyroid hormone levels

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values. METHODS: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals. RESULTS: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values. CONCLUSIONS: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.     

Parasternal block and local anesthetic infiltration with levobupivacaine after cardiac surgery with desflurane: the effect on postoperative pain, pulmonary function, and tracheal extubation times

Early tracheal extubation has become common after cardiac surgery. Anesthetic techniques designed to achieve this goal can make immediate postoperative analgesia challenging. We conducted this randomized, placebo-controlled, double-blind study to investigate the effect of a parasternal block on postoperative analgesia, respiratory function, and extubation times. We enrolled 20 patients having cardiac surgery via median sternotomy; 17 patients completed the study. A de-sflurane-based, small-dose opioid anesthetic was used. Before sternal wire placement, the surgeons performed the parasternal block and local anesthetic infiltration of sternotomy and tube sites with either 54 mL of saline placebo or 54 mL of 0.25% levobupivacaine with 1:400,000 epinephrine. Effects on pain and respiratory function were studied over 24 h. Patients in the levobupivacaine group used significantly less morphine in the first 4 h after surgery (20.8 +/- 6.2 mg versus 33.2 +/- 10.9 mg in the placebo group; P=0.013); they also had better oxygenation at the time of extubation. Four of nine in the placebo group needed rescue pain medication, versus none of eight in the levobupivacaine group (P=0.08). Peak serum levobupivacaine concentrations were below potentially toxic levels in all patients (0.64 +/- 0.43 microg/mL; range, 0.24-1.64 microg/mL). Parasternal block and local anesthetic infiltration of the sternotomy wound and mediastinal tube sites with levobupivacaine can be a useful analgesic adjunct for patients who are expected to undergo early tracheal extubation after cardiac surgery.     

Perioperative interscalene block versus intra-articular injection of local anesthetics for postoperative analgesia in shoulder surgery

BACKGROUND AND OBJECTIVES: Up to 70% of patients report moderate to severe pain after shoulder surgery, which can compromise early rehabilitation and functional recuperation. Postoperative shoulder pain control is improved with both interscalene block and intra-articular local anesthetic injection. The present study hypothesized that perioperative interscalene analgesia would offer pain control superior to perioperative intra-articular local anesthetics over the first 24 hours after surgery. METHODS: Sixty patients undergoing shoulder surgery were randomly assigned to 1 of 2 groups: group IS had interscalene block with catheter installation, while group IA received intra-articular local anesthetic, also with catheter installation. All patients received 3 local anesthetic injections: 0.25 mL/kg of 2% lidocaine with epinephrine 2.5 microg/mL immediately before and after surgery, and 0.25 mL/kg of 0.5% bupivacaine with epinephrine 2.5 microg/mL 1 hour after the end of surgery, after which the catheters were removed, and no further local anesthetics were administered. Postoperative pain at rest was evaluated in the postanesthesia care unit (PACU), 3 hours, 6 hours and 24 hours after surgery. The area under the 24 hour pain over time curve was calculated. Hydromorphone consumption in the PACU and over 24 hours was recorded. RESULTS: Pain scores (IS: 0.4 +/- 2 vs. IA: 4 +/- 3, P < .0001) and opioid consumption (IS: 0.7 mg +/- 1.4 vs. IA: 1.5 mg +/- 1.2, P = .02) were significantly higher in the PACU for group IA. However, neither the mean pain scores over the first day after surgery (IS: 5 +/- 2 vs. IA: 5 +/- 3; P = .4) nor 24-hour opioid consumption (IS: 4.4 mg +/- 2.8 vs. IA: 4.2 mg +/- 2.6; P = .4) were significantly higher in group IA. CONCLUSIONS: PACU measurements of immediate postoperative pain and narcotic consumption favor perioperative interscalene analgesia over intra-articular analgesia. This benefit does not translate into lower overall pain for the first 24 hours after surgery.     

Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction

OBJECTIVE: To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction. DESIGN: Prospective, randomized, placebo-controlled, double-blind, clinical study. SETTING: Cardiothoracic anesthesia department at a university hospital. PARTICIPANTS: Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24). INTERVENTIONS: Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 microg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours. MEASUREMENTS AND MAIN RESULTS: Median plasma concentrations of diltiazem (DTZ group) were 79 microg/L before cardiopulmonary bypass, 67 microg/L at the end of cardiopulmonary bypass, and 164 microg/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. Iohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-beta-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively. CONCLUSION: Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery.     

Lidocaine with fentanyl, compared to morphine, marginally improves postoperative epidural analgesia in children

PURPOSE: To compare the epidural administration of fentanyl (1 microg/mL) combined with lidocaine 0.4% to preservative-free morphine for postoperative analgesia and side effects in children undergoing major orthopedic surgery. METHODS: In a prospective, double-blind study, 30 children, ASA I-II, 2-16-yr-old, were randomly allocated to receive immediately after surgery either epidural F-L (epidural infusion at a rate of 0.1-0.35 mL/kg/hr of 1 microg/mL of fentanyl and lidocaine 0.4%) or epidural M (bolus of 20 microg/kg of morphine in 0.5 mL/kg saline every eight hours). Both groups received 40 mg/kg of iv metamizol (dipyrone) every six hours. In the F-L Group, blood samples were taken on the second and third postoperative day to determine total lidocaine concentrations. Adequacy of analgesia using adapted pediatric pain scales (0-10 score) and side-effects were assessed every eight hours postoperatively. RESULTS: Resting pain scores were under 4, 95% of the time in the F-L Group and 87% of the time in the M Group (Chi square=4.674, P <0.05). The frequency of complications was very similar in both groups. The F-L Group total plasma lidocaine concentrations were directly related to the dose received, and below the toxic range in all patients. CONCLUSIONS: Postoperative epidural fentanyl with lidocaine infusion provides slightly better analgesia than conventional bolus administration of epidural morphine. Side-effects or risk of systemic toxicity were not augmented by the addition of lidocaine to epidural opioids.