Variability of duration of action of neuromuscular-blocking drugs in elderly patients.

BACKGROUND: Steroid-based, non-depolarizing neuromuscular-blocking (NMB) drugs (e.g. rocuronium, vecuronium) are characterized by organ-dependent elimination and significantly longer durations of action in elderly compared to young patients. Cisatracurium is a benzylisoquinolinium NMB drug with a duration of action not altered by ageing. The objective of the study was to determine if elderly patients had less variability in duration of action with 2 x ED95 of cisatracurium compared to equipotent doses of rocuronium or vecuronium. METHODS: Informed consent was obtained from 66 elderly patients with normal renal and liver function. Preoperative midazolam (1 mg) was given IV. The anaesthestic induction was with 5 mg kg(-1) thiopental and 2 microg kg(-1) fentanyl. The patients received 0.6 mg kg(-1) rocuronium, 0.1 mg kg(-1) vecuronium or 0.1 mg kg(-1) cisatracurium. Anaesthetic maintenance was with sevoflurane in oxygen/nitrous oxide. Neuromuscular-blocking duration of action was defined as the return of T1 twitch height to 25% of control. Variability was determined by subtracting the actual duration of action from the mean duration of action for each drug. RESULTS: The durations of action (range, min) were: cisatracurium, 37-81; vecuronium, 35-137; and rocuronium, 33-119. The median of the variability of duration was significantly less with cisatracurium (7 min) compared to vecuronium (18 min) and rocuronium (18 min) (P < 0.05). CONCLUSION: When used with sevoflurane/N(2)O, there was a two-fold greater variability of duration of neuromuscular blockade in elderly patients receiving rocuronium or vecuronium compared with cisatracurium.

Lack of degradation of sevoflurane by a new carbon dioxide absorbent in humans.

BACKGROUND: Potent inhaled anesthetics degrade in the presence of the strong bases (sodium hydroxide or potassium hydroxide) in carbon dioxide (CO2) absorbents. A new absorbent, Amsorb (Armstrong Medical Ltd., Coleraine, Northern Ireland), does not employ these strong bases. This study compared the scavenging efficacy and compound A production of two commercially available absorbents (soda lime and barium hydroxide lime) with Amsorb in humans undergoing general anesthesia. METHODS: Four healthy volunteers were anesthetized on different days with desflurane, sevoflurane, enflurane, and isoflurane. End-tidal carbon dioxide (ETCO2) and anesthetic concentrations were measured with infrared spectroscopy; blood pressure and arterial blood gases were obtained from a radial artery catheter. Each anesthetic exposure lasted 3 h, during which the three fresh (normally hydrated) CO2 absorbents were used for a period of 1 h each. Anesthesia was administered with a fresh gas flow rate of 2 l/min of air:oxygen (50:50). Tidal volume was 10 ml/kg; respiratory rate was 8 breaths/min. Arterial blood gases were obtained at baseline and after each hour. Inspired concentrations of compound A were measured after 15, 30, and 60 min of anesthetic administration for each CO2 absorbent. RESULTS: Arterial blood gases and ETCO2 were not different among three CO2 absorbents. During sevoflurane, compound A formed with barium hydroxide lime and soda lime, but not with Amsorb. CONCLUSIONS: This new CO2 absorbent effectively scavenged CO2 and was not associated with compound A production.

High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane.

PURPOSE: The volatile anesthetic desflurane has been associated with neurocirculatory responses that have been relatively refractory to adjuvant treatment. We have employed desflurane to evaluate the integrity of the sympathetic nerve recording after establishment of the anesthetized state with another anesthetic agent. This retrospective evaluation of data from volunteers determined if higher concentrations of isoflurane that were sufficient to block the neurocirculatory response to laryngeal and tracheal stimulation would abolish the neurocirculatory response to desflurane. METHODS: Data from eight, healthy, young volunteers met our criteria for inclusion. They had been anesthetized with propofol or thiopental and intubated after neuromuscular blockade. Each subject was monitored with radial artery blood pressure (BP), heart rate (HR)(ECG), and sympathetic microneurography. Isoflurane had been administered to achieve a steady state concentration of 1.5 MAC (minimum alveolar concentration) while oxygenation and carbon dioxide were monitored with pulse oximetry and infrared spectrometry, respectively. A deep level of anesthesia was confirmed when laryngoscopy and endotracheal tube movement failed to elicit a neurocirculatory response. A brief exposure to 11% desflurane in the inspired gas was then provided. RESULTS: The responses to desflurane included significant increases in HR, range 32-84 b/min, and BP, range 15-72 mm Hg (P < 0.05). Sympathetic nerve activity increased substantially in the three volunteers with functional nerve recordings. CONCLUSION: In healthy volunteers receiving 1.5 MAC isoflurane, which was sufficient to block the neurocirculatory response to laryngoscopy and tracheal stimulation, there were striking increases in sympathetic outflow, HR and BP when 11% desflurane was substituted for isoflurane.

Absence of bronchodilation during desflurane anesthesia: a comparison to sevoflurane and thiopental.

BACKGROUND: Bronchospasm is a potential complication in anyone undergoing general anesthesia. Because volatile anesthetics relax bronchial smooth muscle, the effects of two newer volatile anesthetics, desflurane and sevoflurane, on respiratory resistance were evaluated. The authors hypothesized that desflurane would have greater bronchodilating effects because of its ability to increase sympathetic nervous system activity. METHODS: Informed consent was obtained from patients undergoing elective surgery with general anesthesia. We recorded airway flow and pressure after thiopental induction and tracheal intubation (baseline) and for 10 min after beginning volatile anesthesia ( approximately 1 minimum alveolar concentration inspired). Respiratory system resistance was determined using the isovolume technique. RESULTS: Fifty subjects were randomized to receive sevoflurane (n = 20), desflurane (n = 20), or thiopental infusion (n = 10, 0.25 mg. kg-1. h-1). There were no differences between groups for age, height, weight, smoking history, and American Society of Anesthesiologists physical class. On average, sevoflurane reduced respiratory resistance 15% below baseline, whereas both desflurane (+5%) and thiopental (+10%) did not decrease respiratory resistance. The respiratory resistance changes did not differ in patients with and without a history of smoking during sevoflurane or thiopental. In contrast, administration of desflurane to smokers resulted in the greatest increase in respiratory resistance. CONCLUSIONS: Sevoflurane causes moderate bronchodilation that is not observed with desflurane or sodium thiopental. The bronchoconstriction produced by desflurane was primarily noted in patients who currently smoked. (Key words: Bronchospasm; respiratory resistance; volatile anesthetics.)

Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions.

This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation, analgesia, cognition, and cardiorespiratory function. Seven healthy young volunteers provided informed consent and participated on three occasions with random assignment to drug or placebo. Heart rate, blood pressure, respiratory rate, ETCO(2), O(2) saturation, and processed electroencephalogram (bispectral analysis) were monitored. Baseline hemodynamic measurements were acquired, and psychometric tests were performed (visual analog scale for sedation; observer's assessment of alertness/sedation scale; digit symbol substitution test; and memory). The pain from a 1-min cold pressor test was quantified with a visual analog scale. After a 10-min initial dose of saline or 6 microg. kg(-1). h(-1) dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 microg. kg(-1). h(-1) dexmedetomidine. Measurements were repeated at the end of infusion and during recovery. The two dexmedetomidine infusions resulted in similar and significant sedation (30%-60%), impairment of memory (approximately 50%), and psychomotor performance (28%-41%). Hemodynamics, oxygen saturation, ETCO(2), and respiratory rate were well preserved throughout the infusion and recovery periods. Pain to the cold pressor test was reduced by 30% during dexmedetomidine infusion. Small-dose dexmedetomidine provided sedation, analgesia, and memory and cognitive impairment. These properties might prove useful in a postoperative or intensive care unit setting. IMPLICATIPNS: The alpha(2) agonist, dexmedetomidine, has sedation and analgesic properties. This study quantified these effects, as well as cardiorespiratory, memory and psychomotor effects, in healthy volunteers. Dexmedetomidine infusions resulted in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise.

Renal responses to low-flow desflurane, sevoflurane, and propofol in patients.

BACKGROUND: The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol. METHODS: Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices. RESULTS: Length of surgery averaged approximately 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 microg x kg(-1) x min(-1). Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal, < 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions. CONCLUSIONS: Alterations in postoperative renal function were common and unrelated to the choice of anesthetic. These findings implicate nonanesthetic factors in producing changes in biochemical indices of renal excretory function.