Pharmacokinetics of cefepime in patients with thermal burn injury.

The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CL(CR)), total clearance (CL(T)), renal clearance (CL(R)), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (V(SS)) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW, respectively. Cefepime CL(T) and CL(R) in burn patients were similar to previously reported values for healthy volunteers when normalized by CL(CR). Stepwise multiple regression was used to associate CL(T) with CL(CR) and days postburn (r(2) = 0.861), CL(R) with CL(CR) and days postburn (r(2) = 0.773), nonrenal clearance with percent third-degree (% 3 degrees ) burn and albumin concentration (r(2) = 0.550), and V(SS) only with % 3 degrees burn (r(2) = 0.624). Simulated steady-state serum concentrations obtained by using the patients' pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h. Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.

Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.

OBJECTIVE: To compare the efficacy, safety, and cost of continuous infusions of lorazepam, midazolam, and propofol in a critically ill trauma/surgery patient population. DESIGN: A prospective, randomized, nonblinded, single center. SETTING: A 16-bed intensive care unit. PATIENTS: A total of 30 ventilated patients who were 18-70 yrs of age and required pharmacologic sedation. Patients with renal and/or liver failure, a history of alcohol abuse, a head injury, or in a coma were excluded. INTERVENTIONS: Patients were randomized by block design to receive lorazepam, midazolam, or propofol. Initial boluses and infusion rates were as follows: lorazepam 0.05 mg/kg, then 0.007 mg/kg/hr; midazolam 0.05 mg/kg, then 0.003 mg/kg/hr; and propofol 0.25 mg/kg, then 0.06 mg/kg/hr. Sedation was assessed and agents titrated every 5-10 mins to achieve > or =2 and <5 on the modified Ramsay scale. Once adequate response was achieved, agents were titrated to maintain the desired level of sedation. MEASUREMENTS AND MAIN RESULTS: Maintenance doses of lorazepam 0.02+/-0.01 mg/kg/hr, midazolam 0.04+/-0.03 mg/kg/hr, and propofol 2.0+/-1.5 mg/kg/hr achieved the desired level of sedation 68%, 79%, and 62% of the time, respectively. Oversedation occurred most often with lorazepam, compared with midazolam and propofol, at 14%, 6%, and 7% of the assessment times, respectively. Undersedation occurred most frequently with propofol compared with lorazepam and midazolam, at 31%, 18%, and 16% of the assessment times, respectively. The mean number of dosage changes per day was 7.8+/-4.3 for lorazepam, 4.4+/-2.9 for midazolam, and 5.6+/-6.0 for propofol (p = .91). Sedation costs per patient day (mean +/- SD) were $48+/-$76 (lorazepam), $182+/-$98 (midazolam), and $273+/-$200 (propofol) (p = .005). The potential savings, if all study patients had received lorazepam, is $14,208 compared with $8,808 if all received midazolam. CONCLUSIONS: The data suggest that lorazepam appears to be a cost-effective choice for sedation; however, oversedation may be problematic. Midazolam is the most titratable drug in our population, avoiding excessive oversedation or undersedation. Trauma patients may respond inadequately to propofol even at higher doses. Lorazepam may be the sedative of choice in critically ill trauma/surgery patients.

Iliac and femoral artery occlusion by thromboemboli from an abdominal aortic aneurysm in the setting of blunt abdominal trauma.

The abdominal aorta is injured infrequently in blunt trauma to the abdomen. When injury does occur, aortic rupture, dissection, and traumatic aneurysm most commonly result. An aneurysmal abdominal aorta would appear to be at increased risk for injury from blunt abdominal trauma. This case report appears to be the first description of iliac and femoral artery occlusion by thromboemboli dislodged from an atherosclerotic abdominal aortic aneurysm at the time of a motor vehicle accident. We believe that this peripheral embolization was caused by direct compression of the abdominal aortic aneurysm by a seatbelt.

Abdominal compartment syndrome.

PURPOSE: Two cases of abdominal compartment syndrome are described and the pathophysiology associated with it is reviewed. CLINICAL FEATURES: The first patient was a 46-yr-old man who sustained extensive blunt abdominal injuries following a fall. The second was a 54-yr-old man involved in a motor vehicle accident with blunt abdominal trauma. In both cases, the patients developed an extremely tense abdomen, increasing peak inspiratory pressures, hypercarbia and oliguria. Both demonstrated improvement in cardiac performance and ventilatory variables following an emergency decompressive celiotomy. CONCLUSION: Abdominal compartment syndrome results in impairment of organ function secondary to increased intraabdominal pressure. These patients require emergency decompressive celiotomy to relieve the symptoms. However, the incidence of intractable asystole and hypotension during this procedure is high and vigilance must be maintained during the release of the increased intraabdominal pressure.

Application of American College of Surgeons' field triage guidelines by pre-hospital personnel.

BACKGROUND: The American College of Surgeons' Committee on Trauma (ACSCOT) has developed field triage guidelines intended to identify seriously injured patients. Unlike the 1990 version, the 1993 revision calls for on-line medical control assistance with the triage decision for patients whose only marker of severe injury is the mechanism of their injury. We prospectively examined the application of the 1990 ACSCOT field triage guidelines to evaluate Emergency Medical Service (EMS) utilization of these guidelines and the potential effects of the 1993 revision. STUDY DESIGN: Emergency Medical Service personnel identified all ACSCOT criteria applicable to patients delivered to the level 1 trauma center at the Medical University of South Carolina. Trauma registry data were used to compare actual injury severity with applicable indicators. Patients with an injury severity score greater than or equal to 16 were considered seriously injured. The South Carolina state trauma and EMS databases were queried to estimate systemwide overtriage and undertriage rates. RESULTS: Questionnaires were completed for 753 patients over 19 months of study. One hundred twenty-two patients had serious injuries. The estimated systemwide overtriage and undertriage rates were 2.7 and 20.3 percent, respectively. Physiologic criteria had a 64.8 percent sensitivity and a 41.8 percent positive predictive value (PPV). The addition of anatomic criteria increased sensitivity to 82.8 percent and decreased PPV to 26.9 percent. Adding mechanism of injury increased sensitivity to 95.1 percent but further reduced PPV to 18.2 percent. Review of EMS records suggests that the addition of on-line medical control for patients in whom only the mechanism of injury triage guidelines apply could improve PPV with little effect on sensitivity. CONCLUSIONS: The current ACSCOT field triage guidelines are appropriate when applied by field EMS personnel.

Application of field triage guidelines by pre-hospital personnel: is mechanism of injury a valid guideline for patient triage?

We prospectively investigated the appropriateness of Mechanism of Injury as an exclusive indicator for trauma center triage. For all patients transported to our level 1 trauma center, EMS personnel identified applicable American College of Surgeons' Committee on Trauma field triage guidelines. A total of 112 questionnaires were completed. Mechanism of injury was the only reason for trauma center transport in 29. Neither intubation nor emergent surgery was required in any of these patients, and all survived. Only two had an ISS > 15. The remaining 83 patients had an 11% mortality rate. Fourteen (16.9%) had ISS scores > 15. Defining an ISS of 16 or greater as severe injury, mechanism of injury alone had a positive predictive value of only 6.9%. Mechanism of injury may not, by itself, justify bypass of local hospitals in favor of trauma centers.

Perfluorocarbons as blood substitutes: the early years. Experience with Fluosol DA-20% in the 1980s.

Clinical testing of perfluorocarbons (PFC) as blood substitutes began in the early 1980's in the form of Fluosol DA-20% (FDA), a mixture of perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F68. We have treated 55 patients (Treatment (T) = 40; Control (C) = 15) with intravenous infusions of 30 cc/kg of FDA as part of either a randomized, clinical trial or a humanitarian protocol. All patients were Jehovah's Witnesses who refused blood transfusion and were severely anemic (mean hemoglobin = 4.6 g/d). FDA successfully increased dissolved or plasma oxygen content (P1O2 in ml/dl), but not overall oxygen content (T group: P1O2 baseline = 1.01 +/- .27, P1O2 12hrs = 1.58 +/- .47 [p = < .0001, t-test]; P1O2 12 hrs: T = 1.58 +/- .47, C = 1.00 +/- .31, p = < .0002, t-test). This effect persisted for only 12 hours post infusion, and had no apparent effect on survival. FDA is an ineffective blood substitute because of low concentration and short half-life. Improved emulsion design may resolve these problems, thereby producing a more effective agent. Our discussion will include a review of our data plus a summary of other reports of FDA efficacy as a blood substitute.

Predictors of mortality in penetrating cardiac injury.

Forty-eight cases of penetrating cardiac trauma seen at the Medical University of South Carolina between 1979 and the present were reviewed retrospectively. Age, race, sex, Champion trauma score, cardiac chamber injured, associated injuries, weapon, circumstances, and means of transport were recorded and analyzed to define predictors of mortality. Overall mortality was 56 per cent. The median trauma score of survivors was significantly higher than the median trauma score of nonsurvivors, P = 0.0001. The median age of survivors was significantly lower than the median age of nonsurvivors, P = 0.046. Sex, race, the chamber injured, weapon, circumstances, and mode of transport were not significantly different between survivors and nonsurvivors. Survival did not change significantly during the study period. Mortality compares favorably with that of other series.

Impact of a major hurricane on surgical services in a university hospital.

Hurricane Hugo struck Charleston, South Carolina, on September 21, 1989. This report analyzes the impact this storm had upon surgical care at a university medical center. Although disaster planning began on September 17, hurricane damage by high winds and an 8.7-foot tidal surge led to loss of emergency power and water. Consequently, system failures occurred in air conditioning, vacuum suction, steam and ethylene oxide sterilization, plumbing, central paging, lighting, and refrigeration. The following surgical support services were affected. In the blood bank, lack of refrigeration meant no platelet packs for 2 days. In radiology, loss of electrical power damaged CT/MRI scanners and flooding ruined patient files, resulting in lost information. In the intensive care unit, loss of electricity meant no monitors and hand ventilation was used for 4 hours. In the operating room, lack of temperature and humidity control (steam, water, and suction supply) halted elective surgery until October 2. Ground and air transportation were limited by unsafe landing sites, impassable roads, and personnel exhaustion. Surgical planning for a major hurricane should include: 1) a fail-safe source of electrical power, 2) evacuation of as many critically ill patients as possible before the storm, 3) cancellation of all elective surgery, and 4) augmented ancillary service staffing with some, although limited, physician support.

The prevalence of hepatitis C in a regional level I trauma center population.

Several studies have examined the prevalence of hepatitis B (HBV) and human immunodeficiency virus (HIV) in a trauma population. To our knowledge, no one has reported on the prevalence of hepatitis C (HCV). We prospectively studied the prevalence of HCV, as well as HBV, HIV, and syphilis in our adult regional level I trauma center population. Two hundred eighty-six consecutive trauma patients were tested for previous exposure to HCV using an anti-HCV mAb ELISA. Patients were also tested for exposure to HBV, HIV, and syphilis, and for illicit drug use. All rho values were calculated using Yates' corrected chi 2 or Student's t test. Twenty-two patients (7.7%) were found to have anti-HCV antibodies, five patients (1.7%) had active HBV, nine patients (3.2%) had HIV, and 16 patients (6%) were positive by RPR. Four (18%) of the patients seropositive for HCV tested positive for HBV, HIV, or syphilis as well. The HIV-positive patients were more likely than the HIV-negative patients to be HCV positive (rho = 0.018). Nine of the HCV seropositive patients (41%) tested positive for cocaine use. Cocaine users were more likely than nonusers to be HCV positive (rho = 0.0007). We have demonstrated the prevalence of HCV in our trauma population to be high (7.7%). It is well known that HCV has a high rate of chronicity, thus up to 90% of these patients are carriers and represent a substantial risk to health care workers. The two significant risk factors, HIV status and cocaine use, are difficult to elicit in the acute setting, reinforcing the need for adhering to universal precautions.

Is hemoglobin level alone a reliable predictor of outcome in the severely anemic surgical patient?

The relationship between outcome and hemoglobin (Hgb), oxygen extraction ratio (ER), history of cardiac, renal, pulmonary, and/or hepatic disease, diabetes, malignancy, sepsis, hypertension, and active bleeding was analyzed in 47 patients with severe anemia (Hgb less than 7.0 gm/dl, mean = 4.6 +/- .2 gm/dl) to evaluate the effect of Hgb on survival and to look for other predictors of outcome. All patients had refused blood transfusion on religious grounds and were participants in a randomized, controlled study of the blood substitute Fluosol DA-20 per cent. Patients were analyzed as a group and after stratifying by Hgb into four levels: (Hgb less than 3.0 gm/dl, N = 7; Hgb less than 3.5 gm/dl, N = 12; Hgb less than 4.0 gm/dl, N = 17; Hgb less than 4.5 gm/dl, N = 23) and by ER into two levels of less than 50 per cent and greater than 50 per cent. Only Hgb, ER, sepsis and active bleeding were predictors of outcome, with sepsis being the only significant, independent predictor of outcome at all levels (P less than .01). Active bleeding was a predictor for levels of Hgb below 4.0 gm/dl. Hgb level alone was a significant predictor only at levels below 3 gm/dl (P less than .05). Extraction ratio interacted with Hgb only below 3 gm/dl (P less than .05). Multiple independent factors influence outcome in the severely anemic patient, the strongest being sepsis and active bleeding. Prevention of sepsis and early intervention to stop bleeding should improve survival in the patient who refuses transfusion.

The failure of serial pneumatic cuff venous occlusion plethysmography to predict patients at risk for pulmonary emboli after trauma.

Over a three month period, attempts to perform serial Pneumatic Cuff Venous Occlusion Plethysmography (VP) were carried out in 51 severely injured patients felt to be at risk for Pulmonary Embolus (PE). Studies could not be performed in 25 of these patients due to the nature of their injuries. Of the remaining 26 patients, two showed evidence of deep vein thrombosis (DVT). Venography confirmed the diagnosis in only one of these patients. Serial VP failed to predict PE in all five patients in whom it was diagnosed. This article concludes that serial VP is not an effective predictor of PE in these patients.

Fluosol DA-20 in the treatment of severe anemia: randomized, controlled study of 46 patients.

We evaluated the safety and efficacy of Fluosol DA-20% (FDA) as a blood substitute in the treatment of severe anemia. Thirty-six patients received either FDA (n = 21) or crystalloid/hydroxyethyl starch (CHS) (n = 15) as part of a randomized, controlled trial. Ten patients received FDA as part of a humanitarian protocol. All were Jehovah's Witnesses who refused transfusion, had bled recently, and had average Hgb levels of 4.3 g/dl. After pulmonary artery catheter insertion, each patient was infused with CHS to attain a pulmonary artery wedge pressure (WP) of 10 to 18 mm Hg. FDA was given as a one-time dose of 30 ml/kg. Data were collected at baseline, 12, 24, and 48 h. None of the patients with negative reactions to a 0.5-ml test dose of FDA had adverse reactions to the subsequent infusion. The plasma or dissolved component of oxygen content was significantly higher in the FDA group at 12 h (FDA group 1.58 +/- 0.47 ml/dl, control group 1.01 +/- 0.31 ml/dl, p less than .02, t-test). Nineteen patients died: 12 (37.5%) FDA, seven (46.6%) control. The difference was not significant. We conclude the following: a) FDA can be given safely to severely anemic patients in doses of 30 ml/kg; b) FDA significantly increased the dissolved component of oxygen content after 12 h but the effect did not persist; c) severely anemic patients can survive without transfusion although mortality is high. In this study, inability of FDA to sustain increased oxygen content was due in part to the rapid elimination of FDA and also to the limited amount given.(ABSTRACT TRUNCATED AT 250 WORDS)

Glutamine and smooth muscle morphology of the gut in rats on total parenteral nutrition.

The purpose of this study was to assess the effects of addition of L-glutamine to an IV nutritional solution on the urinary excretion of 3-methylhistidine (3-MeH) and the morphology of the musculature of the gut in rats. Two experiments were run. In experiment 1 glutamine was added to a mildly hypocaloric IV solution which contained no other amino acids. For experiment 2 glutamine was added to an isocaloric balanced amino acid mixture. In both experiments L-alanine was added in equimolar amounts in place of the L-glutamine for the control groups. Providing glutamine in an IV diet without other amino acids significantly decreased urinary 3-MeH excretion (p less than 0.05). Electron microscopy and morphometric analysis of the jejunum showed an approximate 50% loss of musculature from the gut wall in alanine-treated animals. Glutamine supplementation of a balanced amino acid regime had no effect on urinary 3-MeH excretion or the musculature of the jejunum. We concluded that (1) glutamine is a preferred fuel for jejunal smooth muscle as well as for mucosal cells of the jejunum and (2) only when amino acids are limiting does exogenous glutamine prevent atrophy of the gut musculature.