Outcome assessment in cellulitis clinical trials: is telephone follow up sufficient?

The US Food and Drug Administration has scrutinized clinical trial methodology in cellulitis, partly because the definition and timing of cure are debatable. We analysed the validity of telephone self-report as a proxy for in-person follow up in a cellulitis treatment trial comparing cephalexin alone with cephalexin-plus-trimethoprim/sulfamethoxazole. Our results demonstrate poor agreement between these two methods of outcome determination and have implications for future cellulitis clinical trial design and clinical management.

The electroencephalogram does not predict depth of isoflurane anesthesia.

BACKGROUND: The power spectrum of the electroencephalogram (EEG) may be analyzed to provide quantitative measures of EEG activity (e.g., spectral edge, which defines the highest EEG frequency at which significant activity is found). The current study tested the hypothesis that spectral edge and similar measures distinguish different functional depths of anesthesia in humans. METHODS: Three groups were studied. Group 1 consisted of 34 surgical patients (ASA physical status 1 or 2) who received 0.6, 1.0 and 1.4 MAC isoflurane anesthesia. A subgroup (group 2) of group 1 was tested during 1.0 MAC isoflurane anesthesia at surgical incision. Group 3 consisted of 16 volunteers who listened to an audiotape while receiving 0.15, 0.3, and 0.45 MAC isoflurane or 0.3, 0.45, and 0.6 MAC nitrous oxide in oxygen. The audiotape contained information designed to test implicit and explicit memory formation. We tested the ability of six EEG parameters (spectral-edge, 95th percentile power frequency, median power, and zero crossing frequencies and total power in the alpha- [8-13 Hz] and delta- [< 4 Hz] power ranges) to predict movement after surgical incision, purposeful response to command, or memory of information presented during anesthetic administration. RESULTS: Isoflurane decreased EEG activity in group 1 in a dose-related fashion. The 55% of group 2 who made purposeful movements in response to incision did not differ in their EEG from nonresponders (e.g., spectral edge 19.8 +/- 3.1 vs. 19.3 +/- 2.6 Hz, mean +/- SD). In group 3, memory of the information presented did not correlate with values of any EEG parameter. Response to verbal command was associated with lower anesthetic concentrations and with smaller alpha- and delta-band power (298 +/- 66 vs. 401 +/- 80 watts; and 75 +/- 20 vs. 121 +/- 49 watts, mean +/- SD), but there was no difference in values for other parameters. CONCLUSIONS: We conclude that our EEG measures do not predict depth of anesthesia as defined by the response to surgical incision, the response to verbal command or the development of memory.

No EEG evidence of acute tolerance to desflurane in swine.

Desflurane is a potent inhaled anesthetic associated with a dose-dependent depression of cortical electrical activity. Recently, it has been suggested that the burst suppression pattern seen in dogs given moderately high doses (2.0 MAC) of desflurane may spontaneously subside. This observation suggests the development of acute tolerance to at least some of the anesthetic effects of this drug. No other volatile anesthetic has been found to produce acute tolerance. We attempted to replicate these findings in domestic swine. Five juvenile swine (25-30 kg) were anesthetized with desflurane in oxygen and during normocapnia were exposed to two doses of desflurane sufficient to induce burst suppression (1.5 and 1.7 MAC) for 35 min at each dose, with a period of EEG recovery (0.6 MAC) before, between (in 3 of 5 animals), and after the high doses. Frontoparietal EEG was continuously recorded and the burst suppression ratio continuously calculated. Suppression was more complete at 1.7 MAC than at 1.5 MAC (98.24 +/- 1.75 vs. 90.80 +/- 3.05%, respectively, mean +/- standard deviation). The degree of burst suppression activity did not change over time at either 1.5 (P greater than 0.33) or 1.7 MAC desflurane (P greater than 0.41). There was no EEG evidence of tolerance to desflurane anesthesia in swine.

Arterial washin of halothane and isoflurane in young and elderly adult patients.

We have studied the effect of age on washin of isoflurane and halothane by comparing end-tidal (PE') and arterial (Pa) partial pressures of the agents in young (18-32 yr) and elderly (63-82 yr) healthy patients for 20 min after introduction of the agents, before surgery. PE' was measured by infra-red analysis and Pa by gas chromatography. Washin of isoflurane occurred at the same rate in the young and elderly, with no significant difference between young and elderly in PE' or Pa as proportions of the inspired partial pressure (PI). After 20 min of isoflurane administration, mean Pa/PI in the young was 0.57 (95% confidence limit (CL) 0.53-0.62) and 0.55 in the elderly (95% CL 0.51-0.59). Washin of halothane was slower in the elderly than in the young, with Pa/PI significantly less in the elderly from 10 min after introduction of halothane. The difference between age groups, however, was small: mean Pa/PI after 20 min of halothane administration 0.45 (95% CL 0.41-0.49) in the young and 0.38 (95% CL 0.35-0.41) in the elderly. Washin of isoflurane was significantly faster than that of halothane in both young and elderly subjects. For isoflurane, the PE'-Pa gradient was small relative to Pa and did not differ significantly between young and elderly. For halothane, PE'-Pa in the young did not differ significantly from that for isoflurane. In the elderly, PE'-Pa for halothane was significantly greater than in the young and than PE'-Pa for isoflurane.