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Biomedical subjects

E P Dellinger

Publications and source records attributed to E P Dellinger.

At least 73 records · Page 4Linked to original sources

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

Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 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 (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l 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 less than 0.005) in order to achieve comparable serum concentrations.

Aminoglycosides↗

Effect of clindamycin on growth and haemolysin production by Escherichia coli.

The effect of clindamycin on growth and haemolysin production by four strains of Escherichia coli was tested. Clindamycin MICs were greater than 256 mg/l for all strains. Clindamycin concentrations of 16-256 mg/l significantly inhibited growth, while concentrations from 2-32 mg/l significantly inhibited haemolysin production. Administration of clindamycin to rats with peritonitis due to haemolytic E. coli reduced mortality. Subinhibitory concentrations of clindamycin can inhibit growth and haemolysin production by E. coli and reduce mortality in an animal model of haemolytic E. coli peritonitis.

Animals↗

Importance of unbound phenytoin serum levels in head trauma patients.

Total (bound + unbound) and unbound phenytoin serum concentrations were measured in ten male comatose head trauma patients and ten male epileptic patients. Serum biochemistry and complete blood cell counts were normal for both groups, except albumin concentrations were below normal in the head trauma patients for nutritional reasons. Total phenytoin concentrations were 6.8 +/- 1.8 mcg/ml for the head trauma patients and 14.5 +/- 3.0 mcg/ml for the epileptic patients (p less than 0.0002) even though phenytoin doses were similar. However, unbound phenytoin concentrations were within the therapeutic range of 1 to 2 mcg/ml for both groups and were not significantly different. Had only the total concentrations been measured, phenytoin doses might have been increased inappropriately in the head trauma patients. The reason head trauma patients had therapeutic unbound concentrations despite lower total concentrations was that the unbound per cent of phenytoin was higher in these patients (21 +/- 3.2%) than in the epileptic patients (10 +/- 1.3%, p less than 0.0002).

Adult↗

Anaesthesia in the morbidly obese. A comparison of anaesthetic and analgesic regimens for upper abdominal surgery.

Seventy morbidly obese patients presented for upper abdominal surgery; 17% had pre-existing cardiovascular disease and 23% pre-existing respiratory disease. Twenty-eight patients received general anaesthesia, plus narcotic analgesia postoperatively, and 42 general anaesthesia plus thoracic epidural analgesia intra- and postoperatively. Aspects of anaesthetic management are discussed and compared with previous similar reports. Doses of local anaesthetic for induction of epidural analgesia were less than those for the non-obese but doses of local anaesthetic for maintenance of epidural analgesia were similar to those in non-obese patients. Patients who had thoracic epidural analgesia required less volatile anaesthesia than the group who had general anaesthesia and narcotic analgesics. Postoperative respiratory complications were more common in patients with pre-existing cardiovascular and respiratory disease, and occurred less frequently in patients who had thoracic epidural analgesia.

Abdomen↗

Duration of preventive antibiotic administration for penetrating abdominal trauma.

Eighty-two patients with penetrating abdominal trauma and visceral injuries requiring laparotomy were prospectively randomized to receive either 12 hours or five days of penicillin G potassium and doxycycline hyclate beginning before operation. Distribution between groups was equivalent for all risk factors except shock, which was more prevalent in the 12-hour group. Antibiotics were first administered an average of 64 minutes following injury, and 90% of all patients had received antibiotics and were being operated on within 3 hours 15 minutes. Overall infection rates were 17% in patients with colon penetration, 14% in patients without colon penetration but with other intestinal penetration, and 0% in patients without intestinal penetration. Twelve-hour and five-day antibiotic regimens were comparable in the prevention of postoperative infectious complications following penetrating abdominal injuries. Intestinal penetration was the most important risk factor for developmental of infectious complications in this patient population.

Abdominal Injuries↗

Implications of leukocytosis and fever at conclusion of antibiotic therapy for intra-abdominal sepsis.

Outcomes of 65 patients after operation who had exhibited a clinical response to treatment for intra-abdominal sepsis were compared based on the presence or absence of leukocytosis and fever at the conclusion of antibiotic therapy. Fifty-one patients were afebrile when antibiotics were stopped. Intra-abdominal infection developed in 7 of 21 (33%) who had a persistent leukocytosis, but no intra-abdominal infections developed after operation in 30 patients who had normal WBC counts at the end of antibiotic treatment (p less than 0.005). Nosocomial infections developed in 6 (12%) of the 51 patients, and there was no difference in the incidence between patients with or without leukocytosis. Eleven of 14 (79%) patients who were still febrile when antibiotics were discontinued developed infections after operation. Nosocomial infections occurred in three (21%) and intra-abdominal infections in eight (57%). Of the 15 patients who developed intra-abdominal infection after operation, only four responded to appropriate antibiotic treatment without requiring further surgery. The other patients required surgical management for definitive control within two months of the initial operation. In conclusion, patients at risk of developing infection after operation after exhibiting a clinical response to treatment of intra-abdominal sepsis are those who are afebrile with a persistent leukocytosis or who are still febrile when antibiotics are stopped.

Adult↗

Anergy in high-risk surgical patients: the role of parenteral nutrition.

The finding of delayed hypersensitivity on skin testing has been used to predict the outcome following operations, traumas or severe illnesses and has been correlated with nutritional status in some reports. To test these hypotheses, we did weekly skin tests with a battery of four antigens on 98 high-risk patients referred to the nutritional support service. Anergy persisted or developed in 72 patients, whereas 26 patients remained or became reactive. These two groups were comparable in number of days in hospital, age and amount and duration of parenteral nutrition. Infectious complications (68 percent versus 23 percent, P<.001), sepsis (35 percent versus 12 percent, P<.01) and mortality (33 percent versus 0 percent, P<.001) were more prevalent in anergic than in reactive patients. There was no correlation between nitrogen balance studies and skin test results. In most instances conversion of skin test results occurred as a consequence of appropriate surgical care rather than nutritional support. Whereas nutritional support is required in these high-risk patients, anergy should not be the sole indicator for giving nutritional support or delaying an operation.

Adolescent↗

Gastroplasty in patients with symptoms of reflux esophagitis.

Forty-one patients underwent gastroplasty by the technique of Gomez and has at least one year of follow-up study. Fifteen patients had symptoms of reflux esophagitis preoperatively. At present, only two have symptoms of reflux esophagitis and both were free of symptoms until reversal of the gastroplasty. pH studies of the proximal pouch were performed preoperatively and postoperatively in 14 patients. There was a significant increase in proximal pouch pH after gastroplasty. Following gastroplasty, there is an immediate decrease in acid reflux and symptom reduction is observed to last at least one year. Patients with reflux esophagitis should not necessarily be excluded from consideration for gastroplasty.

Adult↗

Severe necrotizing soft-tissue infections. Multiple disease entities requiring a common approach.

The spectrum of severe soft-tissue surgical infections extends from synergistic necrotizing soft-tissue infections to histotoxic clostridial infections. These syndromes may demonstrate dramatic destruction of underlying tissue far out of proportion to the external evidence for infection, although a marked systemic response in common. The differential diagnosis hinges on the clinical presentation, the Gram's stain, and operative inspection. More important than the precise label placed on a given case is the early recognition of the urgent surgical nature of the infection. Signs indicating a rapidly spreading soft-tissue infection mandate fluid resuscitation, broad-spectrum antibiotics, and early operative exploration with aggressive debridement. These are highly lethal infections in which timely recognition and effective management may be lifesaving.

Aerobiosis↗

Prophylactic antibiotics in surgery: a rationale for the family physician.

Antibiotic administration can effectively reduce the risk of postoperative wound infection under specific circumstances. Maximal protection is obtained when an antibacterial concentration of a bacteriologically appropriate antibiotic regimen is circulating within target tissues at the time of bacterial contamination. This protection is obtained during a finite period, usually not exceeding four hours following bacterial seeding of tissues. The preservation of intact host defense mechanisms is of ultimate importance in preventing wound infection. When defenses are compromised or when an inoculum is of a size that can overwhelm host defenses, the perioperative administration of antibiotics can significantly reduce infection risk. However, antibiotic use must not lead to a relaxation of good surgical judgment and technique.

Anti-Bacterial Agents↗

Leukocytosis at termination of antibiotic therapy: its importance for intra-abdominal sepsis.

Postoperative outcomes of 31 afebrile patients who had responded to treatment for intra-abdominal sepsis were compared based on the presence or absence of leukocytosis (WBC count greater than 10,000/cu mm) at the conclusion of antibiotic therapy. In 68% of the patients who had leukocytosis, postoperative septic complications developed within two months of their operation. In patients without leukocytosis, complications developed in only 8.3%. Afebrile patients who exhibit leukocytosis but have responded clinically to treatment are at risk for postoperative infection and multisystem failure.

Abdomen↗

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.

Adult↗

Determinants of adverse reaction following postoperative T-tube cholangiogram.

The incidence, nature, and mechanisms of adverse reaction following postoperative T-tube cholangiogram have received little attention in the medical literature. This paper presents the experience at one hospital over a 30-month period (1975--1977) covering 139 patients who had 170 cholangiograms. Factors examined included intraoperative and postoperative cultures of bile, the use of antibiotics prior to the performance of the cholangiogram, the technique of cholangiography, the interval between operation and cholangiogram. Eleven (6.5%) cholangiograms were followed by an adverse reaction. Two of these reactions were severe, manifested by signs of septic shock. The administration of antibiotics was not associated with a reduction in adverse reactions. The cholangiographic technique of gravity infusion of dye, which effectively limits the amount of pressure generated during the study, was associated with a significant reduction in adverse reactions. No severe reactions occurred following any study performed by the gravity technique. There was no significant correlation between the age of the patient or the number of days postoperative with adverse reaction. A review of the literature suggests that the mechanism for these severe reactions is cholangiovenous reflux. The avoidance of high intraductal pressures (above 25 cm of water) during the performance of postoperative T-tube cholangiogram should significantly reduce the incidence of adverse reactions.

Adolescent↗

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 treatament groups. Gastric pH was monitored hourly. One hundred twenty-three (85%) patients demonstrated a fall in pH to less than 4 and were considered to require prophylaxis. Prophylaxis was considered adequate if the measured pH could then be maintained at greater than or equal to 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 than placed on hourly administration of antacid with successful elevations of pH to greater than or equal 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 offered 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.

Adult↗

Failure of cimetidine prophylaxis in the critically ill.

Stress ulcers with subsequent hemorrhage are a well-recognized cause of morbidity and mortality in patients hospitalized for other serious illnesses. In 39 critically ill patients, cimetidine was used as a prophylaxis against stress ulcers with the intent to keep the gastric pH level above 4. In 11 of the 39 patients, cimetidine alone did not effect consistent elevation of the gastric pH level above 4. Of the 11 patients, nine had positive blood cultures or clinical infection and five also developed renal failure. Five comatose patients never had pH greater than 4 on cimetidine alone. The mortality for those whose conditions failed to respond to cimetidine was five times greater than for those whose conditions responded to cimetidine. These data imply that a high-risk group of patients can be identified whose conditions may not respond to cimetidine treatment and whose gastric pH must be regularly monitored.

Acute Kidney Injury↗