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Biomedical subjects

M P Shelly

Publications and source records attributed to M P Shelly.

At least 19 recordsLinked to original sources
PubMed1997

Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group.

OBJECTIVE: To determine the therapeutic efficacy and safety of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in the treatment of patients with severe sepsis. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with a planned, midstudy, interim analysis. SETTING: Ninety-one academic medical center intensive care units in North America and Europe. PATIENTS: Patients with severe sepsis or septic shock (n = 696) received standard supportive care and antimicrobial therapy for sepsis, in addition to rhIL-1ra or placebo. INTERVENTIONS: Patients were randomized to receive either rhIL-1ra (100 mg) or placebo (vehicle) by intravenous bolus, followed by a 72-hr continuous intravenous infusion of either rhIL-1ra (2.0 mg/kg/hr) or placebo. MEASUREMENTS AND MAIN RESULTS: The study was terminated after an interim analysis found that it was unlikely that the primary efficacy end points would be met. The 28-day, all-cause mortality rate was 33.1% (116/350) in the rhIL-1ra treatment group, while the mortality rate in the placebo group was 36.4% (126/346), yielding a 9% reduction in mortality rate (p = .36). The patients were well matched at the time of study entry; 52.9% of placebo-treated patients were in shock while 50.9% of rhIL-1ra-treated patients were in shock at the time of study entry (p = .30). The mortality rate did not significantly differ between treatment groups when analyzed on the basis of site of infection, infecting microorganism, presence of bacteremia, shock, organ dysfunction, or predicted risk of mortality at the time of study entry. No excess number of adverse reactions or microbial superinfections were attributable to rhIL-1ra treatment in this study. CONCLUSIONS: A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Adult↗
PubMed1996

The cytokine response to critical illness.

The aims of this review are to provide a basic introduction to the biology of cytokines and to summarise the results of studies, both laboratory and clinical, relating to the cytokine response to critical illness. Elucidation of the cytokine response to conditions such as sepsis, trauma, and burns may be important for several reasons. It may improve understanding of the pathophysiological processes triggered by these insults. It may allow the severity of the insult to be gauged, and maybe even provide prognostic information about individual patients. Similarly it may allow the effectiveness of resuscitation and further treatment to be monitored. Finally, knowing about the cytokine response may provide the key to developing new treatments.

Animals↗
PubMed1995

The management of bereavement on intensive care units.

OBJECTIVE: To investigate the management of the bereaved on Intensive Care Units (ICU) throughout the United Kingdom, and to identify inadequacies that may exist either in the provision of staff training in dealing with bereavement or in the facilities or support available for the bereaved. DESIGN: Questionnaires were sent to the senior nurse and senior doctor in all general ICUs with more than four beds nationwide. The questions asked about nursing and medical practice around the time of a patient's death, as well as about staff attitudes towards, and training in, dealing with bereavement and the support they received for this role. RESULTS: We obtained a 68% (293/430) response rate. Most ICUs had facilities for relatives, but little for the specific needs of the bereaved. Only 6% of doctors and 21% of nurses had training in dealing with bereavement and grieving. A staff support group was available in 23% of ICUs, and 75% of the remainder thought it would be useful to have one. Lack of staff training and poor facilities for relatives were identified as the major concerns of ICU staff. CONCLUSION: Many doctors and nurses working in Intensive Care Units feel inadequately trained to deal confidently with the bereaved. A minority of ICUs have support mechanisms available for their staff, inspite of the perceived need for them. Furthermore, many ICU staff feel the facilities they are able to offer the bereaved are inadequate. We have identified the major inadequacies and the needs of ICU staff for improved training. Meeting these needs would play a significant role not only in reducing staff stress but also minimising the morbidity in surviving relatives.

Bereavement↗
PubMed1992

An active heat and moisture exchanger.

We have carried out a laboratory evaluation of an active heat and moisture exchanging filter (aHMEF). The device consists of a conventional heat and moisture exchanging filter (HMEF) with an additional heating element and water supply. It was compared with a standard HMEF using a model lung. The aHMEF with the heating element alone, reduced 2-hourly water loss compared with the HMEF (P < 0.001); with both the heating element and additional water, this was reduced further (P < 0.001). The mean catheter mount temperature with the HMEF and heater was 32.7 (SD 1.8) degrees C and with the complete aHMEF was 34.6 (1.6) degrees C. The maximum temperature with the heating element in use was 37.7 degrees C. We conclude that the aHMEF provided effective, controllable and convenient humidification of inspired gases.

Evaluation Studies as Topic↗
PubMed1992

The use of sedative agents in critically ill patients.

The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.

Critical Care↗
PubMed1991

The effect on serum lipid concentrations of a prolonged infusion of propofol--hypertriglyceridaemia associated with propofol administration.

Serum concentrations of triglyceride, cholesterol and high density lipoprotein-cholesterol (HDL-cholesterol) were measured in an ICU patient after he had received a 10-day continuous infusion of propofol. No additional parenteral lipid was given in the 72 h prior to initial sampling, but a total of 71 of 10% intralipid had been administered over the remaining 7 days. The total cumulative dose of propofol was 66.1 g (range 0.7-6.4 mg kg-1 h-1). There was no visual appearance of lipaemia. Both the serum triglyceride and cholesterol concentrations increased (triglyceride level increased to 4 times normal whereas the cholesterol elevation was minimal). The HDL-cholesterol concentration decreased. At 72 h after discontinuing the infusion of propofol the triglyceride level remained elevated, the cholesterol concentration had returned to normal and the HDL-cholesterol concentration remained unchanged. The implications of hypertriglyceridaemia are discussed.

Adolescent↗
PubMed1991

Reversible renal failure following opioid administration.

A patient who received intravenous papaveretum during and after operation developed anuria and biochemical evidence of impaired renal function in the first 6 hours after surgery. Administration of naloxone 0.4 mg was associated with a sustained improvement in urine output. Mean arterial pressure did not change significantly. The impairment of renal function may have been related to high plasma concentrations of codeine, one of the constituents of papaveretum.

Acute Kidney Injury↗
PubMed1991

Midazolam infusions in critically ill patients.

Fifty consecutive patients were studied prospectively to assess the effects of a continuous intravenous infusion of midazolam hydrochloride for sedation in patients requiring intensive care. Patient comfort was acceptable in all patients. However, to maintain the same degree of sedation it was necessary to increase the daily dose of midazolam indicating that benzodiazepine tolerance may have been developing. The time taken to awaken following cessation of a midazolam infusion was prolonged in some patients. In those patients with renal failure the mean (+/- SD) value was 44.6 +/- 42.5 h compared to patients without renal failure in whom it was 13.6 +/- 16.4 h (P less than 0.01). Two patients with combined hepatic and renal failure took 124 and 140 h to awaken. Continuous intravenous infusion of midazolam offers good patient comfort but increasing dose requirements in critically ill patients may lead to drug accumulation and delayed awakening. The risks of cumulation may be increased if the drug is given by continuous infusion for prolonged periods without intermittent assessment of the patient's conscious state.

Adolescent↗
PubMed1990

White clot syndrome and continuous arteriovenous haemofiltration.

Severe heparin associated thrombocytopenia is a rare complication of heparin therapy. We report a patient who developed heparin associated thrombocytopenia during continuous arteriovenous haemofiltration and discuss its implications and alternative anticoagulant treatment.

Acute Kidney Injury↗
PubMed1990

Serum acute phase proteins after orthotopic liver transplantation.

Acute phase proteins were measured in six patients before liver transplantation and for 72 h after orthotopic liver transplantation. The ability of the donor liver to mount an acute phase response was demonstrated, although the response was less than that seen in other groups of patients in whom this has been studied. Because of the reduced response to stress, the value of these measurements as indicators of liver function in this group of patients is limited.

Acute-Phase Proteins↗
PubMed1989

Pharmacokinetics of morphine following administration by the buccal route.

The pharmacokinetics of morphine administered via the buccal route as a controlled release formulation were assessed after the administration of three different doses and found to be linear in the dose range 10-30 mg. The plasma concentrations of morphine-3-glucuronide and morphine-6-glucuronide demonstrated considerable inter-subject variation and conclusions could not be drawn regarding their pharmacokinetics. These large differences may reflect not only variability in buccal absorption, but may have resulted from the preparation dissolving in saliva, followed by absorption from the gastrointestinal tract.

Absorption↗
PubMed1989

Pharmacokinetics of morphine in patients following orthotopic liver transplantation.

Plasma and urine concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in seven patients after orthotopic liver transplantation. After a single i.v. bolus of morphine sulphate 10 mg a biexponential decay was observed. Although the distribution and elimination half-lives for morphine were similar to those described in previous studies, a greater total apparent volume of distribution was observed. This was reflected in a greater plasma clearance of morphine than has been reported previously. The concentration of morphine glucuronides remained increased 24 h after administration of morphine; the clinical significance of this remains to be established. The metabolism of morphine was virtually complete, with 4.5% unchanged morphine recovered in urine 24 h after drug administration.

Adult↗