Shahbaz R. Arain

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, ETCO2, O2 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 &mgr;g · kg−1 · h−1 dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 &mgr;g · 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, ETCO2, 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. Implications: The &agr;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.

The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery.

Thirty-four patients scheduled for elective inpatient surgery were randomized equally to receive either dexmedetomidine (initial loading dose of 1-&mgr;g/kg over 10 min followed by 0.4 &mgr;g · kg−1 · h−1 for 4 h) or morphine sulfate (0.08 mg/kg) 30 min before the end of surgery. We determined heart rate (HR), mean arterial blood pressure (MAP), respiratory rate (RR), sedation and analgesia (visual analog scale), and use of additional morphine in the postanesthesia care unit (PACU) and up to 24 h after surgery. Groups were similar for patient demographics, ASA physical status, surgical procedure, baseline hemodynamics, and intraoperative use of drugs and fluids. Dexmedetomidine-treated patients had slower HR in the PACU (by an average of 16 bpm), whereas MAP, RR, and level of sedation were similar between groups. During Phase I recovery, dexmedetomidine-treated patients required significantly less morphine to achieve equivalent analgesia (PACU dexmedetomidine group, 4.5 ± 6.8 mg; morphine group, 9.2 ± 5.2 mg). Sixty minutes into recovery only 6 of 17 dexmedetomidine patients required morphine in contrast to 15 of 17 in the morphine group. The administration of dexmedetomidine before the completion of major inpatient surgical procedures significantly reduced, by 66%, the early postoperative need for morphine and was associated with a slower HR in the PACU.

The Efficacy, Side Effects, and Recovery Characteristics of Dexmedetomidine Versus Propofol When Used for Intraoperative Sedation

We evaluated the cardio-respiratory effects of equi-sedative doses of dexmedetomidine and propofol for intraoperative sedation. Secondary comparison end points were time to achieve and terminate sedation and postoperative analgesia and psychomotor performance. Forty patients scheduled for elective surgery provided informed consent and were randomized equally to receive either dexmedetomidine (1 &mgr;g/kg initial loading dose for 10 min; maintenance, 0.4–0.7 &mgr;g · kg−1 · h−1) or propofol (75 &mgr;g · kg−1 · min−1 × 10 min; maintenance, 12.5–75 &mgr;g · kg−1 · min−1). Hemodynamic variables (heart rate and mean arterial blood pressure), sedation (visual analog scale and Observer Assessment of Alertness/Sedation), bispectral index score of sedation, ventilation (respiratory rate, O2 sat, and ETco2), psychomotor performance (digital symbol substitution test), and pain (visual analog scale) were determined during surgery and up to 95 min after surgery. Intraoperative sedation levels were targeted to achieve a bispectral index score of 70–80. Patient demographics, ASA class, surgical procedure, and baseline cardio-respiratory variables were similar between groups. Sedation was achieved more rapidly with propofol but was similar between groups 25 min after initiating infusions. The average infusion rate for dexmedetomidine was 0.7 &mgr;g · kg−1 · h−1 and 38 &mgr;g · kg−1 · min−1 for propofol. There were no differences between groups in psychomotor performance and respiratory rate during recovery. The previous use of dexmedetomidine resulted in more sedation, lower blood pressure, and improved analgesia (less morphine use) in recovery.

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 (∼ 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.

Sympathetic and vascular consequences from remifentanil in humans.

We explored the possible mechanisms of hypotension during the administration of sedation-analgesia doses of remifentanil in young (ASA physical status I) volunteers (n = 24). Cardiorespiratory and sympathetic variables were collected at baseline and at plasma concentrations of remifentanil (2 and 4 ng/mL). Monitoring included electrocardiogram, heart rate (HR), direct blood pressure, muscle sympathetic nerve activity, and forearm blood flow (FBF). A cold pressor test (1-min hand immersion in ice water) quantified analgesia effectiveness (visual analog scale, 0–100). Visual analog scale to the cold pressor test (62 at baseline) decreased to 27 and 18 during remifentanil infusions. Respiratory rate decreased and end-tidal carbon dioxide (ETCO2) increased with increasing doses of remifentanil; HR, direct blood pressure, muscle sympathetic nerve activity, SpO2 remained unchanged, but FBF increased compared with placebo. In a second study (n = 7), timed respiration was used to maintain ETCO2 during remifentanil, but FBF still increased. In a third study (n = 11), direct effects of remifentanil on vascular tone were determined with progressive infusions from 1 to 100 &mgr;g/h into the brachial artery; FBF increased significantly from 3.5 to 4.3 mL/min per 100 mL of tissue (∼13%–18% increase). Sedative doses of remifentanil resulted in analgesia but no changes in neurocirculatory end-points except FBF. Direct effects of remifentanil on regional vascular tone may play a role in promoting hypotension. IMPLICATIONS: Remifentanil occasionally has been associated with hypotension, the mechanism of which is unclear. This study found that remifentanil directly causes the forearm arterial vasculature to dilate.

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 × ED95 of cisatracurium compared to equipotent doses of rocuronium or vecuronium.

Renal Responses to Low-flow Desflurane, Sevoflurane, and Propofol in Patients

BackgroundThe 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. MethodsInformed 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. ResultsLength of surgery averaged ∼ 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 &mgr;g · kg−1 · 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. ConclusionsAlterations 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.

Desflurane Enhances Reactivity during the Use of the Laryngeal Mask Airway

Background:Desflurane and sevoflurane have markedly different pungencies. The tested hypothesis was that patients breathing equivalent concentrations of desflurane or sevoflurane through a laryngeal mask airway (LMA) would have similar responses. Methods:After institutional review board approval and informed consent were obtained, 60 patients were enrolled and given intravenous midazolam (14 &mgr;g/kg) and fentanyl (1 &mgr;g/kg) 5 min before induction of anesthesia. The LMA was inserted at loss of consciousness after 2 mg/kg propofol. When spontaneous breathing returned, a randomly assigned volatile anesthetic was started at an inspired concentration of either 1.8% sevoflurane or 6% desflurane at a fresh gas flow of 6 l/min in air:oxygen (50:50). After 5 min, a controlled movement of the LMA took place. Three minutes later, the inspiratory anesthetic concentration was changed to either 3.6% sevoflurane or 12% desflurane for 3 min. A blinded observer recorded movements and airway events during the start of anesthetic, LMA movement, deepening of the anesthetic, and emergence before LMA removal. Results:There were no differences at anesthetic start and LMA movement. Desflurane titration to 12% increased heart rate, increased mean arterial blood pressure, and initiated frequent coughing (53% vs. 0% sevoflurane) and body movements (47% vs. 0% sevoflurane). During emergence, there was a twofold greater incidence of coughing and a fivefold increase in breath holding in the desflurane group. Conclusions:When airway responses to sevoflurane and desflurane were compared in elective surgical patients breathing through an LMA, there were significantly more adverse responses with desflurane at 12% concentrations and during emergence.

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.

Vasodilation from Sufentanil in Humans

Sufentanil is a potent opioid that occasionally has been associated with hypotension. The mechanism behind this hypotension is unclear. We hypothesized that sufentanil had a direct effect on vascular smooth muscle to cause vasodilation. Sufentanil was infused into the brachial artery of 10 young, healthy volunteers at rates of 0.083, 0.167, 0.333, and 0.833 &mgr;g/min. Forearm blood flow was measured in both the experimental and control arms with venous occlusion plethysmography. The forearm blood flow in the infused arm increased in a dose-dependent fashion from 3.2 to 5.2 mL/min per 100 mL of tissue whereas simultaneous measurements in the control (non-infused) arm did not increase. Heart rate and mean arterial blood pressure were unchanged during the infusions. Furthermore, respiratory rate did not change at any infusion level and sedation did not occur. Thus, the data support that significant systemic “spillover” of sufentanil did not occur. We conclude that sufentanil has a direct, vasodilatory effect on human vascular tissue that is likely independent of a neurogenic or systemic mechanism.