Titration of sevoflurane anesthesia to optimize the time to regain airway reflexes in patients undergoing elective surgery: A randomized clinical trial comparing desflurane and sevoflurane anesthesia.

BACKGROUND: Desflurane has adverse environmental effects, but has clinical advantages to speed emergence and return of protective airway reflexes compared with sevoflurane. We hypothesized that weaning of the inspired sevoflurane during the final 15 minutes of surgery would eliminate differences in airway reflex recovery between these agents. METHODS: After obtaining IRB approval and informed consent, 40 patients undergoing elective surgery (≥1-hour) randomly received desflurane or sevoflurane. Patients swallowed 20 mL of water without drooling or coughing, and then received sedation and PONV pre-medication. Anesthesia was induced using propofol and fentanyl and maintained with desflurane or sevoflurane through a laryngeal mask airway maintaining a bispectral index of 45-50 and 50-60 during the final 15 minutes before surgery end. Cardiorespiratory variables and age-adjusted minimal alveolar concentration were recorded. The duration between anesthetic discontinuation and first appropriate response to command was measured; the laryngeal mask airway was removed. Two minutes after responding to command, patients were positioned semi-upright and attempted to swallow water. If successful swallowing was not achieved, the test was repeated every 4 minutes after each failure until successful swallowing was achieved. RESULTS: Average anesthetic concentration and bispectral index was similar in patients receiving desflurane vs sevoflurane. Response times after discontinuation of anesthetics were similar. There were no differences in the recovery of swallowing ability between desflurane and sevoflurane groups. CONCLUSION: Weaning of sevoflurane during the final 15 minutes of surgery eliminates clinical advantages of the more rapid return of airway reflexes with desflurane.

Moderate, Short-Term, Local Hyperglycemia Attenuates Forearm Endothelium-Dependent Vasodilation After Transient Ischemia-Reperfusion in Human Volunteers.

OBJECTIVE: Acute hyperglycemia causes endothelial dysfunction in diabetic patients, abolishes ischemic pre- and postconditioning, and is an independent predictor of adverse outcome after myocardial infarction in nondiabetic patients. Its effects on endothelial-dependent vasodilation are controversial in healthy subjects. The authors studied the effect of moderate short-term local hyperglycemia on forearm endothelium-dependent vasodilation in healthy volunteers. DESIGN: Randomized, crossover, blinded, 2-visit, pilot design. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: Five male and 3 female healthy adult volunteers (23±4 years; height 171±13 cm; weight 66±9 kg; [mean±standard error of the mean]). INTERVENTIONS: At each visit, volunteers received an infusion through a brachial artery catheter of either 0.9% saline or dextrose in the experimental, non-dominant arm, to establish mild forearm hyperglycemia. Hemodynamics and forearm blood flow (FBF; plethysmography) were measured at baseline, during brachial artery infusions of acetylcholine in consecutive increments (5, 10, and 15 µg/min), before ischemia (20 min, blood pressure cuff at 200 mmHg), and after 15 minutes of reperfusion. Blood glucose and insulin concentrations were determined from venous samples. The effect of duration of intra-arterial dextrose on FBF was examined. MEASUREMENTS AND MAIN RESULTS: Dextrose increased steady-state blood glucose concentration in the experimental but not the control arm (dominant arm). Dextrose increased FBF compared with saline (4.5±0.5 v 2.6±0.4 mL/min/100 g of tissue, respectively). Acetylcholine caused similar increases in FBF in the absence and presence of dextrose (+239±90% v+203±75%, respectively, during 15 µg/min). The duration of dextrose did not affect this acetylcholine-induced vasodilation. Acetylcholine-stimulated increases in FBF were attenuated in dextrose-treated versus saline after reperfusion (+180±18% v+257±53%, respectively, during 10 µg/min). Interventions in the experimental arm did not affect FBF in the control arm. CONCLUSION: These results indicated that moderate, short-term, local hyperglycemia induced by intra-arterial administration of dextrose attenuated forearm endothelial-dependent vasodilation after ischemia-reperfusion injury in healthy volunteers.

Short-Term Angiotensin Subtype 1 Receptor Blockade Does Not Alter the Circulatory Responses to Sympathetic Nervous System Modulation in Healthy Volunteers Before and During Sevoflurane Anesthesia: Results of a Pilot Study.

OBJECTIVE: The mechanism of perioperative hypotension in patients taking an angiotensin-receptor blocker up to the time of surgery remains unclear. This study tested the hypothesis that short-term angiotensin-receptor blocker treatment attenuated the sympathetic and vascular responses to autonomic stimuli in volunteers undergoing anesthesia. DESIGN: Randomized, crossover, blinded, pilot design. SETTING: Zablocki Veterans Affairs Medical Center, Milwaukee, WI. PARTICIPANTS: The study comprised 8 male and 6 female healthy, young volunteers (age 23±1.2 years [mean±standard error of the mean]). INTERVENTIONS: Volunteers were studied after receiving oral placebo or 50 mg of losartan (angiotensin-receptor blocker) for 3 days before each test day. The effectiveness of angiotensin-receptor blocker treatment was confirmed using the mean arterial blood pressure response to intravenous angiotensin II (1-µg bolus). Eight volunteers underwent direct mean arterial pressure and forearm bloodflow measurements during conscious baseline, a cold pressor test, induction of anesthesia, tracheal intubation, maintenance of anesthesia with 1 minimum alveolar concentration of sevoflurane, and airway irritation with 12% desflurane. Six volunteers experienced mean arterial pressure responses to 0.1 mg of phenylephrine at baseline and during 1 minimum alveolar concentration of sevoflurane. MEASUREMENTS AND MAIN RESULTS: Comparisons were made over time and across groups. Angiotensin-receptor blocker treatment significantly reduced-mean arterial pressure and forearm vascular resistance (forearm blood flow/mean arterial pressure) over time and blocked the mean arterial pressure response to angiotensin-II challenge. The changes in mean arterial pressure and forearm vascular resistance in response to all stressors did not differ between treatments. Mean arterial pressure increases from phenylephrine were preserved. CONCLUSIONS: In healthy, young volunteers, sympathetically-mediated responses from the short-term use of an angiotensin-receptor blocker were not altered and most likely did not contribute to perioperative hypotension during the intraoperative period.

Sevoflurane breakdown produces flammable concentrations of hydrogen.

BACKGROUND: Fires, explosions, and extreme heat production may occur when sevoflurane reacts with desiccated barium hydroxide lime. The identity of the flammable gas has not previously been published, although carbon monoxide, methanol, formaldehyde, and methyl formate have been identified in low quantities. METHODS: The authors reacted sevoflurane with excess desiccated barium hydroxide lime or soda lime at 55 degrees, 100 degrees, 200 degrees, 300 degrees, and 400 degrees C. Formaldehyde, methanol, sodium formate, and hexafluoroisopropanol were reacted with barium hydroxide lime at 300 degrees or 400 degrees C. The authors measured hydrogen production by gas chromatography with a thermal conductivity detector and calculated the molar yield of hydrogen produced. RESULTS: Up to 3 moles of hydrogen were produced per mole of sevoflurane degraded. Each mole of formaldehyde produced up to 2 moles of hydrogen at 400 degrees C. Formate and hexafluoroisopropanol produced up to 1 mole of hydrogen each at 400 degrees C. More than 2 moles of hydrogen were produced by methanol at 400 degrees C. Soda lime and barium hydroxide lime produced similar amounts of hydrogen from sevoflurane above 200 degrees C, but barium hydroxide lime produced more than soda lime at lower temperatures. The temperature above which large amounts of hydrogen were produced seemed to be 300 degrees C. CONCLUSIONS: Up to 3 moles of hydrogen are produced by the chemical reaction of sevoflurane with heated, desiccated absorbent. The high yield, ease of ignition, and low tissue solubility of hydrogen make it the most likely fuel in anesthesia machine fires due to the reaction of sevoflurane with desiccated absorbent.

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 microg/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.

Choice of volatile anesthetic for the morbidly obese patient: sevoflurane or desflurane.

STUDY OBJECTIVE: Morbid obesity is associated with significant comorbidities. Desflurane has a low fat-blood solubility coefficient and may be better suited in this population to achieve a rapid emergence; however, sevoflurane has favorable cardiorespiratory properties that might also prove advantageous in the morbidly obese (MO) patient. This study used careful drug titration to determine if emergence differences between sevoflurane and desflurane could be minimized in MO patients. DESIGN: A randomized, prospective blinded study to determine the emergence profiles of desflurane and sevoflurane in MO patients when anesthetic drug titration is used. SETTING: Operating room of the VA Medical Center, Milwaukee, Wis. PATIENTS: Forty American Society of Anesthesiologists II and III, MO patients (body mass index > or = 35 kg/m2), who were scheduled for elective surgery predicted to last for more than 2 hours, were studied. INTERVENTIONS: Patients were induced with fentanyl, midazolam, and propofol and maintained with desflurane or sevoflurane, mixed in air and oxygen. Intraoperative bispectral index (BIS) was targeted to 45 to 50 and to 60 in the last 15 minutes of surgery. MEASUREMENTS: Intraoperative anesthetic concentration, BIS, and hemodynamics were recorded. During emergence, time to follow command and extubation were noted, with assessments of cognitive function via the Mini-Mental Status Test and psychomotor performance via the Digit Symbol Substitution Test. A blinded observer recorded key recovery events. MAIN RESULTS: Demographic data (age, 61 [36-83] years; body mass index, 38 [35-47] kg/m2), surgical procedures, length of anesthesia (approximately 3.5 hours), adjuvant drugs, and intraoperative BIS, heart rate, and mean arterial pressure were not significantly different. Hemodynamics, time to follow commands and to extubation, and results of Digit Symbol Substitution Test and Mini-Mental Status Test did not differ between anesthetic groups during recovery. CONCLUSIONS: There were no differences in emergence and recovery profiles in MO patients receiving desflurane or sevoflurane when anesthetic concentration was carefully titrated.

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 microg/kg) and fentanyl (1 microg/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.

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

UNLABELLED: Thirty-four patients scheduled for elective inpatient surgery were randomized equally to receive either dexmedetomidine (initial loading dose of 1- microg/kg over 10 min followed by 0.4 microg. 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. IMPLICATIONS: The use of dexmedetomidine for postoperative analgesia resulted in significantly less additional pain medication (morphine) and slower heart rates than a control group receiving only morphine. These outcomes may prove advantageous for patients who might be placed at higher risk by tachycardia or large doses of morphine.

Sympathetic and vascular consequences from remifentanil in humans.

UNLABELLED: 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 (ETCO(2)) increased with increasing doses of remifentanil; HR, direct blood pressure, muscle sympathetic nerve activity, SpO(2) remained unchanged, but FBF increased compared with placebo. In a second study (n = 7), timed respiration was used to maintain ETCO(2) 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 micro g/h into the brachial artery; FBF increased significantly from 3.5 to 4.3 mL/min per 100 mL of tissue (approximately 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.

The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation.

UNLABELLED: 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 microg/kg initial loading dose for 10 min; maintenance, 0.4-0.7 microg. kg(-1). h(-1)) or propofol (75 microg. kg(-1). min(-1) x 10 min; maintenance, 12.5-75 microg. 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 microg. kg(-1). h(-1) and 38 microg. 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. IMPLICATIONS: Dexmedetomidine may be useful for perioperative sedation. It has a slower onset and offset of sedation compared with propofol. Dexmedetomidine was associated with improved analgesia and less morphine use in the postoperative period.

The effects of thiopental and generic and nongeneric propofol on respiratory resistance during anesthetic induction in patients with reactive airways.

STUDY OBJECTIVE: To demonstrate a favorable effect of propofol on respiratory system resistance during anesthetic induction, and to determine if generic propofol causes adverse effects on respiratory resistance. DESIGN: Randomized pilot study. SETTING: Anesthetic induction for elective surgery. PATIENTS: 27 consenting ASA physical status II and III patients with reactive airways (positive smoking history or chronic obstructive pulmonary disease), but not receiving bronchodilator therapy. INTERVENTIONS: Patients were randomized equally to one of three anesthetic induction (and maintenance) drugs: sodium thiopental, 5 mg/kg (25 microg/kg/min), generic or nongeneric propofol, 1.25 mg/kg (50 microg/kg/min). They received preinduction midazolam and fentanyl (2 mg and 150 microg) and intravenous lidocaine (0.5 mg/kg). After anesthetic induction, tracheal intubation was established, and predetermined settings for mechanical ventilation were initiated. MEASUREMENTS: Immediately after intubation, a sensor was placed on the 8-mm endotracheal tube to detect baseline airway pressure and flow. During maintenance, repeat measurements of pressure and flow were obtained at 2.5-minute intervals for 10 minutes. Respiratory system resistance was derived off-line using the isovolumetric technique. MAIN RESULTS: Patients were similar across groups. The respiratory resistance measured after anesthetic induction did not differ among groups. During the maintenance infusion of thiopental or propofol, respiratory resistance increased gradually across all groups. There was no difference in the response of respiratory resistance either at induction or during the 10-minute maintenance between the generic and the nongeneric propofol groups. CONCLUSIONS: In contrast to earlier reports, this pilot study was unable to document a difference in the respiratory resistance in patients induced with thiopental or propofol. In addition, we were unable to demonstrate any different respiratory responses between generic propofol, containing sodium metabisulfite preservative, and nongeneric propofol.

Vascular responsiveness to brachial artery infusions of phenylephrine during isoflurane and desflurane anesthesia.

UNLABELLED: Compared with equi-minimum alveolar anesthetic concentration (MAC) isoflurane, desflurane is associated with greater levels of sympathetic nerve activity in humans but similar reductions in blood pressure. To explore these divergent effects, we evaluated vascular alpha(1)-adrenoceptor responses in the human forearm during isoflurane and desflurane anesthesia to determine if alpha(1)-adrenoceptor responses were more substantially attenuated during desflurane administration. Bilateral forearm venous occlusion plethysmography was used to examine arterial blood flow and to determine changes in forearm vascular resistance during brachial artery infusions of saline and phenylephrine (0.2, 0.4, 0.8, and 1.6 microg/min) in 22 conscious subjects and during anesthesia with 0.65 and 1.3 MAC isoflurane or desflurane. Infusion of phenylephrine into the brachial artery increased the forearm vascular resistance in a dose-dependent manner. The arterial response to phenylephrine was significantly attenuated by 0.65 and 1.3 MAC desflurane and similarly attenuated during 1.3 MAC isoflurane (P < 0.05). Impaired arterial alpha(1)-adrenoceptor responsiveness occurred during desflurane. However, this effect was statistically similar (P > 0.05) to the impaired responses during isoflurane. Blood pressure decreases during volatile anesthesia may be, in part, caused by decreased alpha(1)-adrenoceptor responsiveness. IMPLICATIONS: alpha-receptors on blood vessels regulate constriction and dilation and therefore modulate blood pressure. This research indicates that vasoconstriction via the alpha(1)-receptor vascular response is impaired during isoflurane and desflurane anesthesia.