Amir Darvish

The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery

The prophylactic antiemetic efficacy of intravenous (IV) ondansetron, droperidol, perphenazine, and metoclopramide was evaluated in a prospective, doubleblind study of 360 ASA physical status I-III patients undergoing total abdominal hysterectomy (TAH). Subjects were randomized to receive IV, one of ondansetron 4 mg, droperidol 1.25 mg, perphenazine 5 mg, metoclopramide 10 mg, or placebo prior to induction of anesthesia. Hypotension immediately after administration of metoclopramide was observed in two patients and four patients given ondansetron developed profound systolic hypotension at induction of anesthesia. Twenty-two percent of patients receiving droperidol became sedated. Postoperatively, patients developing severe nausea, retching, or vomiting, defined as severe emetic sequelae (SES), were deemed to have failed antiemetic prophylaxis and received antiemetic rescue. A significantly larger number of patients who received IV ondansetron (63%), droperidol (76%), and perphenazine (70%) were free of SES when compared to placebo (43%); P < 0.05. Metoclopramide was ineffective. Although ondansetron, droperidol, and perphenazine were effective in providing antiemetic prophylaxis, only IV perphenazine was free of side effects. Hence, we conclude that perphenazine is the best choice for antiemetic prophylaxis after TAH. (Anesth Analg 1995;81:139-43)

Inhaled albuterol, but not intravenous lidocaine, protects against intubation-induced bronchoconstriction in asthma

BackgroundThe ability of intravenous lidocaine to prevent intubation-induced bronchospasm is unclear. The authors performed a prospective, randomized, double-blind, placebo-controlled trial to test the ability of intravenous lidocaine and inhaled albuterol to attenuate airway reactivity after tracheal intubation in asthmatic patients undergoing general anesthesia. MethodsSixty patients were randomized to receive either 1.5 mg/kg intravenous lidocaine or saline, 3 min before tracheal intubation. An additional 50 patients were randomized to receive 4 puffs of inhaled albuterol or placebo 15–20 min before tracheal intubation. Anesthesia was induced with propofol. Immediately after intubation and at 5-min intervals, transpulmonary pressure and airflow were recorded, and lower pulmonary resistance (RL) was calculated. Isoflurane was administered after the initial two measurements to assess reversibility of bronchoconstriction. A bronchoconstrictor response to intubation was defined as RL greater than or equal to 5 cm H2O · l−1 · s−1 in the first two measurements after intubation and RL subsequently decreasing by 50% or more after isoflurane. ResultsThe lidocaine and placebo groups were not different in the peak RL before administration of isoflurane (8.2 cm H2O · l−1 · s−1vs. 7.6 cm H2O · l−1 · s−1) or frequency of airway response to intubation (lidocaine 6 of 30 vs. placebo 5 of 27). In contrast, the albuterol group had lower peak RL (5.3 cm H2O · l−1 · s−1vs. 8.9 cm H2O · l−1 · s−1;P < 0.05) and a lower frequency of airway response (1 of 25 vs. 8 of 23;P < 0.05) than the placebo group. ConclusionsInhaled albuterol blunted airway response to tracheal intubation in asthmatic patients, whereas intravenous lidocaine did not.

Heterogeneous Vasomotor Responses of Rabbit Coronary Microvessels to Isoflurane

BackgroundPrevious in vitro studies on the mechanism of isoflurane-elicited vasodilation have examined conductance arteries and reported conflicting data on whether the vasomotor response Is mediated through the release of endothelium-derived nitric oxide. The current study was undertaken to define the effect of isoflurane on both resistance and conductance coronary arteries in rabbits and to elucidate the mechanism of the effect. MethodsRabbit coronary arteries of varying sizes were dissected and each placed in a microvessel chamber. The arteries were studied in a pressurized (40 mmHg), no-flow state and were exposed to increasing concentrations of isoflurane, 0–3%, by an in-line bubble-through vaporizer. The vessel lumen diameter was monitored using an optical density video detection system. Selected experiments were performed on micro-vessels after preincubation with indomethacin, NG-monomethyl-L-arginine, or methylene blue or after endothelial denudation. ResultsIsoflurane caused a dose-dependent constriction of small rabbit coronary arteries (internal diameter of 139 ± 34 μ, mean ± SD), whereas it caused dilation of large coronary arteries (371 ± 54 μ). The vasoconstriction of the small coronary arteries by isoflurane was abolished by endothelial denudation or after preincubation with indomethacin. The vasodilation of the large vessels by isoflurane was inhibited by endothelial denudation or after preincubation with NG-monomethyl-L-arglnine, methylene blue, or indomethacin. ConclusionsOur data suggest that vessel size is a determinant of the vasomotor response to isoflurane. Exposure to isoflurane produces vasodilation of conductance coronary arteries, whereas it is associated with vasoconstriction of resistance coronary microvessels. The latter appears to be endothelium-dependent and mediated by cyclooxygenase produces), whereas the former, also endothelium-dependent, is mediated by both product(s) of cyclooxygenase and endothelium-derived nitric oxide.

Isoflurane and halothane attenuate endothelium-dependent vasodilation in rat coronary microvessels.

Volatile anesthetics attenuate endothelium-dependent vasodilation but the mechanism of attenuation remains controversial. The present study examines the mechanism of isoflurane- and halothane-mediated attenuation of endothelium-dependent vasodilation in Wistar rat coronary microvessels of about 100 micro m internal diameter. The vessels were studied in vitro in a pressurized (40 mm Hg), no-flow state using video microscopy. After preconstriction of the vessels with the thromboxane analog U46619 1 micro M, concentration response curves to acetylcholine (ACh), the calcium ionophore A23187, sodium nitroprusside (SNP), or the stable cyclic guanosine monophosphate (cGMP) analog 8-bromo-cGMP (Br-cGMP) were obtained in the presence of 0% (control), 1% or 2% isoflurane, or 1% or 2% halothane. Isoflurane 1% and 2% significantly attenuated vasodilation to ACh and A23187. Isoflurane 2%, but not 1%, attenuated vasodilation to SNP. Vasodilation to Br-cGMP was not affected by isoflurane. Halothane attenuated vasodilation to ACh, but had no effect on vasodilation to A23187, SNP, or Br-cGMP. We conclude that isoflurane attenuates endothelium-dependent vasodilation by impairing at least two distinct steps in the nitric oxide (NO)-cGMP pathway, the first being between endothelial increase of calcium and smooth muscle guanylate cyclase and the second being inhibition of soluble guanylate cyclase activity. These two steps appear to have different sensitivities to the effect of isoflurane. Halothane has an effect at the endothelial receptor level, but not any distal steps in the NO-cGMP pathway. (Anesth Analg 1997;84:278-84)

Oxygen-derived free radicals mediate isoflurane-induced vasoconstriction of rabbit coronary resistance arteries.

Isoflurane induces endothelium-dependent constriction of rabbit coronary resistance arteries in vitro. This effect is inhibited by the cyclooxygenase inhibitor indomethacin. To determine whether thromboxane or oxygen-derived free radicals, a byproduct in the cyclooxygenase pathway, mediate this effect, subepicardial coronary arterioles (103 +/- 21 mu) from New Zealand White rabbits were studied in vitro in a pressurized (40 mm Hg), no-flow state using videomicroscopy. The vessels were subjected to increasing concentrations of isoflurane, 0%-3%, in the presence of Dazmegrel (a specific inhibitor of thromboxane synthesis; Pfizer Ltd., Sandwich, UK) or SOD-Mn (manganese superoxide dismutase, a scavenger of superoxide radicals) or mannitol (hydroxyl radical scavenger) 20 or 100 mM or in their absence (control). The control vessels showed a concentration-dependent constriction to isoflurane (P < 0.0001), with reduction in internal diameter of 11.4% +/- 3.5% at isoflurane 3%. This response was unaffected by Dazmegrel (P = 0.78), but was abolished by SOD-Mn (P < 0.01) or mannitol (P < 0.01). We conclude that isoflurane causes concentration-dependent constriction of rabbit coronary resistance arteries and that this effect is mediated by oxygen-derived free radicals. (Anesth Analg 1995;80:1163-7)

Isoflurane Attenuates cAMP-Mediated Vasodilation in Rat Microvessels

BACKGROUND Endothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation. METHODS AND RESULTS Fifty-three subepicardial coronary arteries (diameter, 103 +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L, concentration response curves to the nonselective beta-adrenergic agonist isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence of absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls. CONCLUSIONS Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.