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Biomedical subjects

J E Peacock

Publications and source records attributed to J E Peacock.

At least 19 recordsLinked to original sources
PubMed1992

Rapid intravenous infusion of amphotericin B: a pilot study.

PURPOSE: The administration of amphotericin B in the conventional prolonged infusion over 4 to 6 hours is complicated by the acute toxicities of fevers and chills in 50% to 90% of patients and the chronic toxicities of increased creatinine levels and hypokalemia in 60% to 80% of patients. To determine the safety and toxicity of rapid infusions, we conducted a prospective, nonrandomized study in patients with clinical indications for antifungal therapy. PATIENTS AND METHODS: Twenty-five granulocytopenic adults with acute leukemia and myelodysplastic syndromes were enrolled in a phase I trial using four sequentially shorter infusion durations: a standard infusion over 4 hours (n = 3) and shortened infusion durations at 3 hours (n = 3), 2 hours (n = 4), and 1 hour (n = 15). Toxicity was assessed by daily examinations of study subjects by one of the study investigators, by documentation of all infusion-related fevers and chills, and by daily monitoring of serum levels of creatinine, potassium, magnesium, and aspartate aminotransferase. RESULTS: Temperatures greater than 38 degrees C occurred in 16 of 25 (64%) patients, but only two had temperatures exceeding 40 degrees C. Chills were observed in 13 of 25 (56%) patients, but only one had severe symptoms. Serum creatinine increased more than 0.5 mg/dL (44.20 mumol/L) above the pretreatment baseline in 17 of 25 (68%) patients, and the absolute creatinine level was greater than or equal to 2.0 mg/dL (176.8 mumol/L) in 10 of 25 (40%) patients. Serum potassium levels dropped below the normal limit of 3.5 mEq/L (3.5 mmol/L) in all patients, but no patient had potassium levels below 2.5 mEq/L (2.5 mmol/L). Intravenous potassium supplementation was administered to all patients and exceeded 100 mEq/d in 12 of 25 (48%) patients. CONCLUSIONS: Rapid infusions of amphotericin B are safe, are associated with similar toxicity as prolonged infusions, and facilitate inpatient care by decreasing nursing time needed for administration and minimizing scheduling conflicts with other necessary intravenous medications. Shorter infusions also facilitate outpatient and home administration of amphotericin B.

Aged↗
PubMed1992

Infusion of propofol to identify smallest effective doses for induction of anaesthesia in young and elderly patients.

We studied 110 patients older than 60 yr or aged 18-50 yr as separate groups in two stages to identify the smallest effective doses of propofol for induction of anaesthesia. In the elderly patients, in stage 1, at infusion rates of 25, 50 or 100 mg min-1 the mean (SD) doses administered were propofol 0.82 (0.14) mg kg-1, 1.22 (0.24) mg kg-1 and 1.65 (0.60) mg kg-1 and the induction times 140.1 (21.9) s, 103.2 (23.5) s and 69.4 (10.0) s, respectively. In stage 2, after induction with a fixed dose of 0.82 mg kg-1 as a bolus over 5 s or as an infusion at 25 mg min-1, the times for induction were 38.5 (14.0) s and 144.5 (36.6) s, respectively. In the young patients, at induction rates of 33.3, 50, 100 or 200 mg min-1, the doses administered were propofol 1.36 (0.28) mg kg-1, 1.46 (0.12) mg kg-1, 1.85 (0.43) mg kg-1 and 2.39 (0.50) mg kg-1 and the induction times 145.0 (25.4) s, 120.0 (18.4) s, 80.2 (19.2) s and 54.5 (10.4) s, respectively. In stage 2, a fixed induction dose of 1.46 mg kg-1 resulted in induction times of 35.0 (8.5) s and 134.0 (26.8) s, respectively. In stage 2 of each age group, induction was achieved with smaller doses than those recommended previously and there was no difference in the number of patients in whom induction of anaesthesia was successful or in the measured cardiorespiratory variables between the two induction regimens. This suggests the latter effects are caused by the dose administered and not the rate of administration.

Adolescent↗
PubMed1992

Addition of rifampin to combination antibiotic therapy for Pseudomonas aeruginosa bacteremia: prospective trial using the Zelen protocol.

A multicenter, prospective randomized trial was conducted to determine if the addition of rifampin to a combination therapy of an antipseudomonal beta-lactam agent and aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the experimental therapy (rifampin+). If the experimental therapy was refused, the patient would then receive the standard combination therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal antibiotics, neutropenia, severity of illness, and presence of pneumonia. Fifty-eight patients were randomized to receive rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a beta-lactam agent plus an aminoglycoside. Sixty-three received the standard therapy of a beta-lactam plus an aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing bacteremias occurred in 2% of the three-drug (rifampin+) group, compared with 14% for the two-drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups. Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of antimicrobial agents.

Aged↗
PubMed1991

Prolonged continuous acyclovir treatment of normal adults with frequently recurring genital herpes simplex virus infection. The Acyclovir Study Group.

In this 3-year study of suppressive acyclovir for recurrent genital herpes, patients with more than six recurrences per year were randomized initially to 400 mg of acyclovir or placebo orally two times per day, with recurrences treated with 200 mg of acyclovir five times per day for 5 days. In the second year of the study, all patients received acyclovir as a daily suppressive or intermittent acute therapy; in the third year, all received daily acyclovir. Among 525 patients completing 3 study years, 289 received 3 years of suppressive therapy and 236 received 1 year of acute therapy followed by 2 years of suppressive therapy. Of those who completed the third year, 61% were recurrence free that year; 25% of the suppressive therapy-only group were recurrence free for all 3 years. The annual recurrence rate dropped from more than 12 recurrences per year at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy) recurrences during the third year. No significant toxic effects were detected. Daily suppressive acyclovir therapy was effective and well tolerated.

Acyclovir↗
PubMed1991

Effectiveness of preoxygenation in morbidly obese patients.

The time taken for the oxygen saturation (SpO2) to decrease to 90% after preoxygenation was studied in six morbidly obese patients and six matched controls of normal weight. During apnoea the obese patients maintained Spo2 greater than 90% for 196 (SD 80) s (range 55-208 s), compared with 595 (SD 142) s (range 430-825 s) in the control group (P less than 0.001). One patient in the obese group had desaturation before the onset of complete relaxation and tracheal intubation, without complications. Bedside lung function tests were not significantly different between groups and cannot be used as a predictor of the effectiveness of preoxygenation.

Carbon Dioxide↗
PubMed1990

Interaction of granulocytopenia and construction activity as risk factors for nosocomial invasive filamentous fungal disease in patients with hematologic disorders.

A clinicoepidemiologic study was undertaken to investigate an apparent increase in frequency of nosocomial invasive filamentous fungal disease (NIFFD) in adult patients with acute leukemia hospitalized during a period of hospital construction, and to determine if a relationship existed between the construction activity and the acquisition of NIFFD. The first study goal, to determine the incidence of NIFFD before and during construction, was approached by calculation of incidence rates of NIFFD in patients with acute leukemia, comparing 1982 and 1983 (a baseline period free of construction) to 1986 (a year when construction activity was at its peak). The second study goal, to identify risk factors for the development of NIFFD, was accomplished by reviewing the autopsy records of all patients with underlying hematologic disorders accompanied by granulocytopenia who died in our hospital from 1982 through 1986. Patients with and without autopsy evidence of NIFFD were then compared by univariate and multivariate (logistic regression) analysis to identify potential risk factors for the acquisition of NIFFD. The incidence of NIFFD in patients with acute leukemia hospitalized during the period of hospital construction was significantly increased when compared to a baseline period without construction (11 per 139 versus 4 per 333, p less than .001). Review of all granulocytopenic patients autopsied over the five-year interval 1982 through 1986 revealed duration of granulocytopenia and hospitalization during construction to be risk factors for NIFFD by univariate analysis (p less than .005). Logistic regression showed duration of granulocytopenia to be highly significant independent risk factor (p less than .01) and construction activity to be a probable independent risk factor (p = .09).(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗
PubMed1990

Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients.

The effect of changing the rate of infusion of propofol for induction of anaesthesia was studied in 60 elderly patients. Propofol was administered at 300, 600 or 1200 ml h-1 until loss of consciousness (as judged by loss of verbal contact with the patient) had been achieved. The duration of induction was significantly longer (P less than 0.001) with the slower infusion rates (104, 68 and 51 s), but the total dose used was significantly less (P less than 0.001) in these patients (1.2, 1.6 and 2.5 mg kg-1, respectively). The decrease in systolic and diastolic arterial pressure was significantly less in the 300-ml h-1 group at the end of induction and immediately after induction (P less than 0.01). The incidence of apnoea was also significantly less in the slower infusion group.

Aged↗
PubMed1990

Pharmacokinetics of an infusion of propofol during cardiac surgery.

We have measured whole blood concentrations and pharmacokinetics of propofol administered as a constant rate infusion during cardiac surgery. Ten patients undergoing elective cardiac surgery involving cardiopulmonary bypass (seven myocardial revascularization and three aortic valve surgery) received a continuous infusion of propofol 4 mg kg-1 h-1 to supplement alfentanil analgesia. Whole blood propofol concentrations were measured by high pressure liquid chromatography. A concentration greater than 1 microgram ml-1 was achieved within 15 min of starting the infusion and remained constant throughout surgery. Volume of distribution, clearance and terminal half-life were similar to those found in non-cardiac patients.

Adolescent↗
PubMed1990

The Ohmeda 9000 syringe pump. The first of a new generation of syringe drivers.

The Ohmeda 9000 syringe pump was developed in response to the need for an infusion apparatus to administer intravenous anaesthetic agents. It incorporates a bolus facility for the rapid, controlled delivery of loading infusions, or incremental dosing over a background maintenance infusion, and may be interfaced with a controller for computer-driven infusions. The Ohmeda 9000 pump has undergone bench testing and detailed evaluation in clinical practice using a variety of syringe sizes and makes. It is capable of accurate delivery over a range of infusion rates provided the recommended manufacturers' syringes are used with the appropriate pump setting. The pump was easy to use and reliable in clinical research and routine clinical practice. It should find its niche as the first genuinely 'anaesthetist-friendly' infusion pump.

Anesthesia, Intravenous↗
PubMed1990

Persistent neutrophilic meningitis.

Persistent neutrophilic meningitis is an unusual but distinct clinical variant of chronic meningitis characterized by CSF neutrophilia with hypoglycorrhachia which persists for more than 1 week on serial CSF studies. Documented etiologies include selected bacteria and higher bacteria such as Brucella, Nocardia and Actinomyces as well as "opportunistic" fungi such as Candida, Aspergillus, the Zygomycetes, and Pseudallescheria. Recognition of the syndrome is important, as empiric therapy (e.g., cotrimoxazole and amphotericin B) may differ significantly from that used for classic chronic meningitis.

Chronic Disease↗
PubMed1990

Amphotericin B revisited: reassessment of toxicity.

PURPOSE: Although amphotericin B remains the mainstay of therapy for serious fungal infections, numerous acute and chronic toxicities make clinical usage difficult. Nevertheless, utilization of amphotericin B has increased dramatically in recent years. Accordingly, a study to reassess toxicity associated with the use of amphotericin in the modern era and to determine the aggregate impact toxicities have on the overall therapeutic course of patients was undertaken. PATIENTS AND METHODS: The charts of 50 patients at our institution who had received amphotericin B were retrospectively reviewed for the occurrence of drug-related acute and chronic toxicities and their impact on therapy. Patients evaluated were at least 21 years of age, had received at least 100 mg of amphotericin B, and were treated for at least 3 days. An analysis to investigate associations between drug administration variables and toxicities was also undertaken. RESULTS: The mean age of study subjects were 54 years, the average duration of therapy was 19 days, and the mean cumulative dose of amphotericin B was 582 mg. Acute toxicities accompanying infusion occurred in 66% of all patients. Fever was experienced by 34% of study subjects and chills by 56%, with rates of 2.6 and 3.5 mean episodes per patient per treatment course, respectively. Other acute toxicities including hypotension were rare, and no patients exhibited bronchospasm or anaphylaxis. Nephrotoxicity occurred in 30 patients (60%). Baseline creatinine values in these patients rose by a mean of 1.55 mg/dL (137 mumol/L), with increases in creatinine ranging from 0.2 to 5.2 mg/dL (18 to 460 mumol/L). Analysis of six drug administration parameters by stepwise multiple linear regression failed to reveal any significant associations with nephrotoxicity. The mean nadir potassium value was 3.1 mEq/L (3.1 mmol/L) (range: 2.3 to 4.8 mEq/L [2.3 mmol/L]), with 45 of 50 patients (90%) receiving potassium supplementation (average daily supplement = 69 mEq). Only increasing amphotericin B concentration was correlated with an increased requirement for potassium supplementation (p less than 0.01, stepwise multiple linear regression). CONCLUSION: Although clinically important toxicities continue to occur with usage of amphotericin B despite current methods of infusion and premedication, these are usually manageable and rarely limit the course of therapy.

Adult↗
PubMed1989

Prospective, randomized comparison of sequential intravenous followed by oral ciprofloxacin with intravenous ceftazidime in the treatment of serious infections.

In a prospective, comparative trial, 47 hospitalized patients with serious infections that required parenteral antibiotic therapy were randomly assigned to receive either ciprofloxacin (200 mg every 12 hours intravenously followed by 500 mg every 12 hours orally at a time dependent on the patients' clinical and bacteriologic responses) or ceftazidime (2 g every eight to 12 hours intravenously). All evaluable subjects (39 patients) had documented infections, 23 percent of which were associated with bacteremia. The mean/median duration of intravenous antibiotic use for ciprofloxacin was 7.37/five days and for ceftazidime 9.95/seven days; 63 percent of the ciprofloxacin patients received an additional 17 days of oral therapy with ciprofloxacin, whereas intravenous therapy with ceftazidime was followed by an average of 12 days of an oral regimen in 55 percent of patients. Overall response rates for patients receiving ciprofloxacin and ceftazidime were 76 percent (16 of 21) and 82 percent (18 of 22), respectively. Four out of five bacteremias in each group were successfully treated. Overall, 69 percent of the pathogens were gram-negative aerobes, and 47 percent of the infections involved the urinary tract. Failure of therapy was most often associated with pneumonia (two of five failures with ciprofloxacin and three of four failures with ceftazidime). Adverse effects occurred in approximately 20 percent of patients in each group and were mild and reversible. Superinfections occurred in five of 19 (26 percent) ciprofloxacin recipients and seven of 20 (35 percent) ceftazidime recipients. All fungal superinfections involved the genitourinary tract and occurred most often in association with chronic indwelling catheters. Enterococcal superinfections occurred in both groups (a bacteremic urinary tract infection in a ceftazidime patient and osteomyelitis in a ciprofloxacin patient). Clostridium difficile-associated diarrhea was documented in a ceftazidime recipient. The mean duration of hospitalization following the onset of antibiotic treatment was 10.45 days in the ciprofloxacin group and 12.95 days in the ceftazidime group. Sequential intravenous/oral ciprofloxacin was as safe and effective as intravenous ceftazidime in the treatment of infections due to susceptible gram-positive and gram-negative organisms.

Administration, Oral↗
PubMed1989

Transdermal fentanyl for the relief of pain after upper abdominal surgery.

Transdermal fentanyl (n = 22) was compared with placebo (n = 18) in a double-blind study of pain after upper abdominal surgery. All patients also received i.v. morphine on demand for supplementary analgesia. The transdermal systems were applied 2 h before induction of anaesthesia and remained in situ for 24 h. After operation, pain scores were significantly lower and peak expiratory flow rates significantly higher in the transdermal fentanyl group, who demanded significantly less morphine than the control group. Mean plasma fentanyl concentrations at 12 and 24 h were within the therapeutic range (1.5 and 2.0 ng ml-1, respectively).

Abdomen↗
PubMed1989

The safety of dental extractions in patients with hematologic malignancies.

Dental disorders have been recognized as major sources of infection in patients with hematologic malignancies (HM). Management of severe dental infections usually includes dental extractions (DE), but the safety of extractions in patients with HM who are at risk for bleeding, sepsis, and poor wound healing has not been well established. In conjunction with an aggressive program of dental care, 142 DE were performed in 26 patients with acute leukemia, myelodysplastic syndromes, and myeloproliferative disorders. Granulocytopenia (less than 1,000 granulocytes/microL) was present during or within ten days following surgery in 14 patients. In these 14 patients (101 DE), the mean granulocyte count was less than 450/microL, with a median duration of granulocytopenia following surgery of 32 days (range, four to 169 days). Thrombocytopenia (less than 100,000 platelets/microL) occurred during or within two days following surgery in 13 patients (80 DE), with a mean platelet count of 63,500/microL. Transfusions were given for platelet counts less than 50,000/microL. All DE were performed without significant complications. Bleeding was minor to moderate and easily controlled with local measures; no patient required transfusion due to hemorrhage. Average maximum temperature 24 hours after DE was 37.7 degrees C. No episodes of bacteremia were documented within ten days of DE. Minor delay in wound healing was observed in two patients. We conclude that DE can be safely performed in patients with HM in combination with aggressive supportive care.

Agranulocytosis↗