David Simonowitz

Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients

SummaryAminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (>90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). The results were similar for all 3 drugs. Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.31 and 135.8 ml/min for gentamicin, 29.01 and 162.4 ml/min for tobramycin, and 26.81 and 157.3 ml/min for amikacin) than in normal weight patients (17.01 and 95.9 ml/min for gentamicin, 18.31 and 101.3 ml/min for tobramycin, and 18.61 and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p<0.005) in order to achieve comparable serum concentrations.

Randomized prospective evaluation of cimetidine and antacid control of gastric pH in the critically ill

One hundred forty-four critically ill patients admitted to an intensive care setting were randomly assigned to cimetidine or antacid treatment groups. Gastric pH was monitored hourly. One hundred twenty-three (85%) patients demonstrated a fall in pH to <4 and were considered to require prophylaxis. Prophylaxis was considered adequate if the measured pH could then be maintained at ≥4. Fifty-eight patients received antacids alone, the average requirement being 41 cc/hour. Sixty-five patients received cimetidine. Seventeen (26%) of the cimetidine prophylaxis patients failed to raise their pH and were then placed on hourly administration of antacid With successful elevations of pH to ≥4 in all cases on an average supplementary dose of 53 cc/hour. Risk factors, including sepsis, hypotension, head injury, respiratory failure, degree of trauma, and age, were not statistically different in the two treated groups. Using these same criteria, responders to cimetidine could not be differentiated from nonresponders. All patients were protected from significant stress bleeding while on this study. Significant complications of either treatment were minimal. Antacids ottered consistent protection against gastric acidity and were 100% effective. A routine schedule of 300 mg every six hours of cimetidine was effective in only 47% of patients, and the maximum dose of cimetidine was effective in only 74% of patients. Hourly measurement of intragastric pH is required for monitoring the response to prophylaxis of stress bleeding in severely ill patients.

EFFECT OF ACUTE ETHANOLISM ON THE HOSPITAL COURSE AND OUTCOME OF INJURED AUTOMOBILE DRIVERS

Acute ethanolism in automobile drivers is purported to be both protective and detrimental in susceptibility to injury from an accident. The potential influence of acute intoxication (serum ethanol greater than 100 mg/dl) on pattern and severity of injury, hospital course, and long-term outcome, including mortality, was examined in 182 consecutive automobile drivers requiring admission to a regional university trauma center during 1980. Significantly more drivers were intoxicated than not, 61% vs. 39%. Similarly, more than 75% of the intoxicated drivers were young males and more than 80% of the intoxicated drivers were felt to be negligent and at cause for the accident. However in this series, the patterns and severity of injuries, hospital course, and late outcome were unaffected by the patients blood alcohol level. Acute alcohol intoxication apparently neither protected nor hindered the response to injury in these motor vehicle drivers.

Boerhaave syndrome. Successful conservative management in three patients with late presentation

Three patients with Boerhaave syndrome were successfully managed with nonoperative treatment. The diagnosis was delayed 5 days in one patient and 10 days in the other two. None of the patients appeared septic. Their conditions had been misdiagnosed as myocardial infarction, pneumonia and pulmonary embolism. Treatment consisted of intravenous hyperalimentation and administration of antacids and antibiotics. Cimetidine was also used in one patient. Two patients were discharged 14 days after diagnosis and the third on the 20th hospital day. Follow-up barium swallows showed complete healing in 2 months in all three patients. Conservative management of spontaneous esophageal perforation is feasible when (1) the perforation is already 5 days old, (2) there are no signs of severe sepsis, (3) esophageal barium study shows a wide-mouthed cavity draining freely back into the esophagus, and (4) the pleural space is not contaminated. When the diagnosis is made promptly, surgical therapy remains the treatment of choice, and patients managed conservatively who show signs of sepsis should be operated on without hesitation. Follow-up esophageal evaluation should be performed to confirm complete healing and to evaluate underlying disease.

Cimetidine clearance in the obese

Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t½ was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady‐state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.

Gastric pH monitoring as a prognostic indicator for the prophylaxis of stress ulceration in the critically III.

Previous studies have documented the efficacy of prophylaxis in the prevention of stress ulceration and bleeding in critically ill patients. In an effort to determine whether all critically ill patients require prophylaxis, 144 patients admitted to an intensive care unit were monitored by continuous indwelling nasogastric or gastrostomy tubes. Any patient with a measured gastric pH of less than 4 was treated with prophylactic cimetidine or antacids to maintain a pH of 4 or greater. One hundred twenty-three (85 percent) met this criterion. The gastric pH of 21 patients (15 percent) never fell below 4 during continuous monitoring for 26+/- 4.2 hours. There was a significantly lower incidence of hypotension and respiratory failure in this group ( pl < 0.05). Mortality was higher in the patients who required prophylaxis (15 percent) than in those who did not (0 percent). No bleeding was encountered in any patient in either group. These data suggest that patients who do not require prophylaxis may be determined by continuous monitoring of intragastric pH. If, within 24 hours, intragastric pH does not fall below 4, minimal indications for prophylaxis exist. Intragastric pH monitoring is a simple, effective tool in the care and management of critically ill or traumatized patients.

Diagnostic considerations in acute alcoholic and gallstone pancreatitis.

Comparison of a group of patients with acute alcoholic pancreatitis with a group with gallstone pancreatitis has established the serum amylase level on admission as one of the most useful laboratory tests in aiding to differentiate the two entities. A serum amylase level greater than 1,500 IU was most often due to gallstone pancreatitis, as was elevation of the serum bilirubin and alkaline phosphatase levels.

Natural history of incidental appendectomy in patients with Crohn's disease who required subsequent bowel resection

The records of 20 patients with Crohns disease who underwent incidental appendectomy and later required bowel resection were reviewed and the following conclusions ascertained. If the patient had had abdominal pain for less than 1 week, appendectomy is followed by minimal problems. If the patient has had abdominal pain for longer than 1 week, incidental appendectomy is followed by an 83 percent incidence of fistula or sinus tract, arising not from the appendiceal stump but from the terminal ileum. The natural history of patients with resection after appendectomy includes more medication and a higher symptom recurrence rate and perhaps operative recurrence rate than their counterparts who have not undergone incidental appendectomy.

Use of Op Site as an Occlusive Dressing for Total Parenteral Nutrition Catheters

A retrospective study of standard hyperalimentation catheter dressing compared to the use of Op Site has demonstrated that Op Site is cost and time effective and is efficacious for attaining a low catheter sepsis rate. It is easy for nursing personnel to apply and comfortable for the patients to wear. Op Site may be contraindicated in diaphoretic patients.

Inflammatory tissue reaction in rabbit bowel injected with Crohn's homogenates☆

Homogenates from the terminal ileum of a patient with Crohns disease with granulomas were prepared as snap-frozen or fresh and were injected into the ascending colonic walls of New Zealand white rabbits. Control animals were injected with 1 per cent bovine serum albumin alone. The rabbit bowel was examined after 1 year, and lesions were noted in each of the rabbits injected with Crohns disease homogenate, irrespective of the type of tissue preparation. The observed lesions were diffuse and occurred both at the injection site and in the terminal ileum. These changes were not noted in the control group. This work confirms earlier results in the same animal model and suggests that either fresh or snap-frozen homogenates will produce the intestinal lesion but that bovine albumin alone will not.