Alfentanil during rapid sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg: tracheal intubation conditions.

BACKGROUND: Opioids have become an integral part of anaesthesia induction. We aimed to determine the dose of alfentanil needed to obtain perfect tracheal intubation conditions during rapid sequence induction with standard doses of thiopental and rocuronium, where laryngoscopy was initiated 55 s after commencement of drug administration. The influence of covariates (sex, body weight, age, alfentanil plasma concentration at laryngoscopy) was tested. METHODS: Eighty-four healthy individuals were randomly assigned to receive one of the seven assessor-blinded alfentanil doses (0, 10, 20, 30, 40, 50 and 60 µg/kg) in conjunction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. For drug administration, 15 s was allowed. Laryngoscopy was initiated 40 s after rocuronium and tracheal intubation concluded within 70 s after commencement of drug administration. Alfentanil doses associated with 50%, 90% and 95% probability of perfect intubation conditions were determined with logistic regression. Multiple logistic regressions were used to test the influence of covariates. The relationship between alfentanil dose and concentration at laryngoscopy was analysed with linear regression. The effects of covariates on plasma concentrations of alfentanil were tested with multiple linear regressions. RESULTS: Perfect intubation conditions of 95% probability was obtained with 56 µg/kg (confidence intervals 44-68). None of the covariates were significant predictors of perfect intubation conditions. Alfentanil plasma concentration correlated with dose and increased with increasing body weight (1.7 ng/ml/kg). CONCLUSION: Perfect intubation conditions during rapid sequence induction can be obtained with clinically relevant doses of alfentanil in most healthy patients anaesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

Sex-related differences in the relationship between acceleromyographic adductor pollicis train-of-four ratio and clinical manifestations of residual neuromuscular block: a study in healthy volunteers during near steady-state infusion of mivacurium.

BACKGROUND: Studies in volunteers suggest that train-of-four (TOF) ratios >0.9 are needed to retain normal function of muscles involved in upper airway patency, swallowing, and vital capacity breathing. We determined if sex-related differences exist in the relationship between adductor pollicis (AP) TOF ratio and measures of neuromuscular function commonly used to assess recovery from neuromuscular block. METHODS: In 10 males and 10 females, three steady-state levels of neuromuscular block were achieved with mivacurium infusions. TOF ratio was measured with acceleromyography at the AP. Hand grip strength and the ability to clench the teeth, raise the head >5 s, swallow, protrude the tongue, and open the eyes were tested at each stable block level and reconciled to uncorrected and normalized (pre-paralysis values) TOF measures. These relationships were compared between sexes. RESULTS: The ability to clench teeth and head raise >5 s was lost at a significantly greater TOF ratio in males than females. The percentage decrease in handgrip strength with decreasing TOF ratio was proportionally greater in males than females. Forty per cent of the males were unable to clench the teeth at an uncorrected TOF ratio >0.9. When TOF ratios were normalized, clinical functions showed no decrement at TOF ratio >0.9 in any volunteer. CONCLUSIONS: Sex-related differences exist in the relationship between AP TOF ratio and clinical measures of muscle function used to assess recovery from neuromuscular block. Normalization of AP TOF ratios is recommended because a non-normalized TOF ratio of 0.9 does not guarantee adequate reversal of neuromuscular block.

Interactive effects of pH and temperature on N-methyl-D-aspartate receptor activity in rat cortical brain slices.

Low extracellular pH decreases the activity of the N-methyl-D-aspartate (NMDA) glutamate receptor, and may thus limit neuronal calcium overload during cerebral ischemia. During induced hypothermia, alkaline pH ("alphastat regulation") is often used to preserve cardiac and enzymatic function. The purpose of this study is to measure the functional activity of cerebral cortex NMDA receptors over the range of temperatures used in profound hypothermic cardiopulmonary bypass (20-37 degrees C). Extracellular pH was varied over a broad range relevant to both alphastat and pH stat acid-base management (7.0-7.8). Change in cytosolic free calcium evoked by 50 microM NMDA in brain slices was used as an index of NMDA receptor activity. Cortical slices (300 microns thick) were loaded with fura-2 Aspartate Methyl for study in a fluorometer. At 37 degrees C, a change in extracellular pH from 7.1 to 7.8 increased the NMDA-evoked change in cytosolic calcium in brain slices by a factor of 4 (p < 0.05). In contrast, at 20 degrees C there was minimal effect of changing extracellular pH from 7.1 to 7.8 (27% increase). We conclude that hypothermia results in decreased pH sensitivity of the NMDA receptor. The results predict that different strategies of pH management during induced hypothermia may have limited impact on NMDA receptor-mediated processes, such as neuronal calcium overload.

Volatile and intravenous anesthetics decrease glutamate release from cortical brain slices during anoxia.

BACKGROUND: Extracellular accumulation of the excitatory neurotransmitter L-glutamate during cerebral hypoxia or ischemia contributes to neuronal death. Anesthetics inhibit release of synaptic neurotransmitters but it is unknown if they alter net extrasynaptic glutamate release, which accounts for most of the glutamate released during hypoxia or ischemia. The purpose of this study was to determine if different types of anesthetics decrease hypoxia-induced glutamate release from rat brain slices. METHODS: Glutamate released from cortical brain slices was measured fluorometrically with the glutamate dehydrogenase catalyzed formation of the reduced form of nicotinamide adenine dinucleotide phosphate. Glutamate release was measured in oxygenated (PO2 = 400 mmHg), hypoxic ((PO2 = 20 mmHg), and anoxic ((PO2 = 20 mmHg plus 100 microM NaCN) solutions and with clinical concentrations of anesthetics (halothane 325 microM, enflurane 680 microM, propofol 200 microM, sodium thiopental 50 microM). The source of glutamate released during these stresses was defined with toxins inhibiting N and P type voltage-gated calcium channels, and with calcium-free medium. RESULTS: Glutamate released during hypoxia or anoxia was 1.5 and 5.3 times greater, respectively, than that evoked by depolarization with 30 mM KCl. Hypoxia/anoxia-induced glutamate release was not mediated by synaptic voltage-gated calcium channels, but probably by the reversal of normal uptake mechanisms. Halothane, enflurane, and sodium thiopental, but not propofol, decreased hypoxia-evoked glutamate release by 50-70% (P < 0.05). None of the anesthetics alter basal glutamate release. CONCLUSIONS: The authors conclude that halothane, enflurane, and sodium thiopental but not propofol, at clinical concentrations, decrease extrasynaptic release of L-glutamate during hypoxic stress.

Hypoxic ventilatory response predicts the extent of maximal breath-holds in man.

To understand the factors influencing breath-holding performance, we tested whether the hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) were predictors of the extent of maximal breath-holds as measured by breath-hold duration, the lowest oxyhemoglobin saturation (SpO2min), lowest calculated PaO2 (PaO2min) and highest end-tidal PCO2 (PETCO2max) reached. Steady state isocapnic HVR and hyperoxic HCVR were measured in 17 human volunteers. Breath-holds were made at total lung capacity (TLC), at TLC following hyperventilation, at functional residual capacity, and at TLC with FIO2 = 0.15. SpO2 was measured continuously by pulse oximetry, and alveolar gas was measured at the end of breath-holds by mass spectrometry. PaO2min was calculated from SpO2min and PETCO2max. HVR was a significant predictor of both SpO2min and PaO2min. HVR and forced vital capacity were predictors of breath-hold duration by multiple linear regression. HCVR had no significant predictive value. We conclude that HVR, but not HCVR, is a significant predictor of breath-holding performance.

Productivity versus availability as a measure of faculty clinical responsibility.

UNLABELLED: Faculty clinical time is an extremely valuable commodity. Most departments quantify faculty clinical time on an "availability" basis (e.g., number of days in the operating room or nights on call). We hypothesize that a productivity measure (i.e., determination of actual clinical care delivered rather than availability of such care) would produce different results than the availability system. The "billable hour" was chosen as the measurement device. It was defined as time that anesthesia was actually given, as obtained from the anesthetic record. After collecting data for a year, we found that despite parity using the availability system, the billable hour system detected significant differences between faculty within and between groups. We conclude that "availability" and "productivity" systems produce different conclusions regarding the relative contributions of an individual faculty or subspecialty group. IMPLICATIONS: Accountability of clinical activities by faculty is crucial to the financial status of any department of anesthesia. We hypothesized that methods of availability (e.g., amount of time scheduled for clinical activities) versus productivity measure (actual amount of clinical care delivered) would be quite different between faculty and differing subspecialty groups. Even though the availability system distributed clinical time on an equal basis, there was a wide difference of clinical productivity within and between specialty groups. We conclude that a productivity measure (i.e., billable hours) is a more accurate reflection of faculty productivity than an availability system and is more in line with departmental sources of financial income.

Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers.

BACKGROUND: Because of the rapid recovery of neuromuscular function after succinylcholine administration, there is a belief that patients will start breathing sufficiently rapidly to prevent significant oxygen desaturation. The authors tested whether this belief was valid. METHODS: Twelve healthy volunteers aged 18-45 yr participated in the study. After preoxygenation to an end-tidal oxygen concentration greater than 90%, each subject received 5 mg/kg thiopental and 1 mg/kg succinylcholine. Oxygen saturation (SaO2) was measured at both a finger and an ear lobe (beat to beat). During the period of apnea and as they were recovering, the volunteers received continuous verbal reassurance by the investigators. If the SaO2 decreased below 80%, the volunteers received chin lift and, if necessary, assisted ventilation. The length of time the subject was apneic and level of desaturation were related by linear regression analysis. One hour after recovery and again 1 week later, subjects were asked a series of questions regarding their emotional experience. RESULTS: In six volunteers, SaO2 decreased below 95% during apnea; in four, SaO2 decreased below 80%, necessitating chin lift and assisted ventilation in three. Apnea time was significantly longer in volunteers who reached SaO2 less than 80% than in those who did not (7.0+/-0.4 and 4.1+/-0.3 min, respectively), and there was a significant correlation between the length of time the subject was apneic and the magnitude of desaturation. CONCLUSIONS: Spontaneous recovery from succinylcholine-induced apnea may not occur sufficiently quickly to prevent hemoglobin desaturation in subjects whose ventilation is not assisted.

Acute severe isovolemic anemia impairs cognitive function and memory in humans.

BACKGROUND: Erythrocytes are transfused to prevent or treat inadequate oxygen delivery resulting from insufficient hemoglobin concentration. Previous studies failed to find evidence of inadequate systemic oxygen delivery at a hemoglobin concentration of 5 g/dl. However, in those studies, sensitive, specific measures of critical organ function were not used. This study tested the hypothesis that acute severe decreases of hemoglobin concentration alters human cognitive function. METHODS: Nine healthy volunteers, age 29 +/- 5 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and after acute isovolemic reduction of their hemoglobin to 7, 6, and 5 g/dl and again after transfusion of their autologous erythrocytes to return their hemoglobin concentration to 7 g/dl. To control for duration of the experiment, each volunteer also completed the same tests on a separate day, without alteration of hemoglobin, at times of the day approximately equivalent to those on the experimental day. RESULTS: No test showed any change in reaction time or error rate at hemoglobin concentration of 7 g/dl compared with the data at the baseline hemoglobin concentration of 14 g/dl. Reaction time, but not error rate, for horizontal addition and digit-symbol substitution test (DSST) increased at hemoglobin 6 g/dl (mean horizontal addition, 19%; 95% confidence interval [CI], 4-34%; mean DSST, 10%; 95% CI, 4-17%) and further at 5 g/dl (mean horizontal addition, 43%; 95% CI, 6-79%; mean DSST, 18%; 95% CI, 4-31%). Immediate and delayed memory was degraded at hemoglobin 5 g/dl but not at 6 g/dl. Return of hemoglobin to 7 g/dl returned all tests to baseline, except for the DSST, which significantly improved, and returned to baseline the following morning after transfusion of all autologous erythrocytes. CONCLUSION: Acute reduction of hemoglobin concentration to 7 g/dl does not produce detectable changes in human cognitive function. Further reduction of hemoglobin level to 6 and 5 g/dl produces subtle, reversible increases in reaction time and impaired immediate and delayed memory. These are the first prospective data to demonstrate subtle degraded human function with acute anemia of hemoglobin concentrations of 6 and 5 g/dl. This reversibility of these decrements with erythrocyte transfusion suggests that our model can be used to test the efficacy of erythrocytes, oxygen therapeutics, or other treatments for acute anemia.