摘要:

BackgroundIntrathecally administered adenosine receptor agonists have antinociceptive effects in animals, suggesting that intrathecal adenosine might provide analgesia in humans. The authors performed preclinical neurotoxicity studies to define the safety of intrathecally administered adenosine in rats and dogs.MethodsEighteen rats with long‐term intrathecal catheters received daily injections of saline or 100 &mgr;g adenosine for 4 days and were observed for general behavior and thermal nociception before being killed on day 6. Nine beagle dogs were prepared with long‐term, lumbar intrathecal catheters and infused continuously with saline or adenosine, 2.4 mg/day for 48 h, then 7.2 mg/day for 26 days. Animals were then anesthetized and perfused with preservative and their spinal cords were examined systematically.ResultsNo disturbances in neurologic function were detected in either animal species. intrathecal adenosine caused transient sedation in rats and increased muscle tone in dogs, resolving with continued exposure to drug. Neither adenosine‐ nor saline‐treated rats or dogs showed acute thermal analgesia. Adenosine groups did not differ from saline groups regarding histopathology, although a moderate fibrotic and inflammatory reaction was noted in both, and protein concentrations in cerebrospinal fluid were increased in both.ConclusionThe current study in rats and dogs failed to provide behavioral or histologic evidence of neurotoxicity from intrathecal administration of adenosine. This provides evidence for the presumption of safety of adenosine in this dose range, and supports phase I safety trials of acute intrathecal adenosine administration in humans.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe hypermetabolic state induced by acute endotoxemia and malignant hyperthermia (MH) may be indistinguishable. The aims of this study were (1) to investigate the differences between MH and sepsis, (2) to determine whether acute endotoxemia can trigger MH, and (3) to establish the effects of dantrolene in these two disorders.MethodsThree groups of swine were studied. All pigs were invasively monitored and initially anesthetized with nontriggering agents. A placebo MH‐susceptible group (n = 5) received normal saline whereas the endotoxin groups (MH‐susceptible, n = 6; MH‐negative, n = 4) received intravenous endotoxin (250 &mgr;g/kg total) during 2.5 h. Halothane (1.5%) and succinylcholine (2–4 mg/kg) were then administered, followed by two doses of dantrolene (4 mg/kg total).ResultsEndotoxin infusion resulted in pulmonary hypertension and systemic hypotension in pigs with and without the MH mutation, but did not trigger MH. Halothane and succinylcholine triggered MH, evidenced by a markedly higher oxygen consumption in the MH‐susceptible pigs that received endotoxin (325 ± 196 ml/min) and those that did not (374 ± 110 ml/min) compared to the MH‐negative pigs (69 ± 15 ml/min,P< 0.0009), as well as muscular rigidity in the susceptible animals. Dantrolene reversed these changes. Three of the six MH‐susceptible pigs that received endotoxin died; two died soon after triggering and one after dantrolene administration. In contrast, none of the MH‐negative pigs or the MH‐susceptible pigs that did not receive endotoxin died (0 of 9vs. 3 of 6,P= 0.044).ConclusionEndotoxemia does not trigger MH, but may worsen outcome if it occurs.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundThe authors used continuous quality improvement (CQI) program data to investigate trends in quality of anesthesia care associated with changing staffing patterns in a university hospital.MethodsThe monthly proportion of cases performed by solo attending anesthesiologistsversusattending–resident teams or attending–certified registered nurse anesthetist (CRNA) teams was used to measure staffing patterns. Anesthesia team productivity was measured as mean monthly surgical anesthesia hours billed per attending anesthesiologist per clinical day. Supervisory ratios (concurrency) were measured as mean monthly number of cases supervised concurrently by attending anesthesiologists. Quality of anesthesia care was measured as monthly rates of critical incidents, patient injury, escalation of care, operational inefficiencies, and human errors per 10,000 cases. Trends in quality at increasing productivity and concurrency levels from 1992 to 1997 were analyzed by the one‐sided Jonckheere‐Terpstra test.ResultsProductivity was positively correlated with concurrency (r = 0.838;P< 0.001). Productivity levels ranged from 10 to 17 h per anesthesiologist per clinical day. Concurrency ranged from 1.6 to 2.2 cases per attending anesthesiologist. At higher productivity and concurrency levels, solo anesthesiologists conducted a smaller percentage of cases, and the proportion of cases with CRNA team members increased. The patient injury rate decreased with increased productivity levels (P= 0.002), whereas the critical incident rate increased (P= 0.001). Changes in operational inefficiency, escalation of care, and human error rates were not statistically significant (P= 0.072, 0.345, 0.320, respectively).ConclusionsMost aspects of quality of anesthesia care were apparently not effected by changing anesthesia team composition or increased productivity and concurrency. Only team performance was measured; the role of individuals (attending anesthesiologist, resident, or CRNA) in quality of care was not directly measured. Further research is needed to explain lower patient injury rates and increases in critical incident reporting at higher concurrency and productivity levels.

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1999

数据来源: OVID