Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.     

Precipitate formed by thiopentone and vecuronium causes pulmonary embolism

Purpose

To examine the effects of a bolus injection of the precipitate formed by thiopentone and vecuronium on the pharmacokinetic behaviour of thiopentone, cardiopulmonary physiology, and lung histology.

Methods

Of 16 female rabbits (2.9 to 3.1 kg), eight were injected with a precipitate formed by a mixture of 5 mg·kg^?1 thiopentone and 0.67 mg·kg^?1 vecuronium via the external jugular vein. Eight control rabbits were injected with 5 mg·kg^?1 thiopentone alone. Plasma thiopentone concentration, systolic arterial pressure and PaO₂ were measured for 60 min after injection. Histological changes in the lungs were evaluated at one and 60 min.

Results

Maximum blood thiopentone concentration in the precipitate group was lower than in the control group (12.9 ± 4.5 vs 17.0 ± 1.6 μg·ml,P < 0.05), although the half-life of thiopentone in the precipitate group was longer (32.3 ± 8.5 vs 21.7 ± 8.2 min.P < 0.05) and the area under the time concentration curve was similar between the two groups. However, the mean residence time was 28% longer in the precipitate group than in controls (P < 0.05). The PaO₂ was lower in the precipitate group than in controls one minute after injection (431 ± 27 vs 464 ± 18 mmHg,P < 0.05) but not subsequently. Histologically, crystals (30–150 μm in diameter) obstructed small arteries in the lungs at one minute but not at 60 min after injection.

Conclusion

Intravenous injection of precipitate causes pulmonary microembolism, with a small transient decrease in PaO₂     

Heparin and protamine titration do not improve haemostasis in cardiac surgical patients

Purpose

Weight-based heparin and protamine dosing strategies for cardiopulmonary bypass (CPB) do not take into account interpatient variability in drug sensitivity and may result in bleeding complications. We compared the Hemochron® RxDx heparin and protamine titration system with standard weight based management with regard to heparin dose, protamine dose, and perioperative bleeding.

Methods

One hundred and thirty-five cardiac surgical patients were randomised into four groups. Group I received standard heparin and protamine management: Group 2 received heparin and protamine byin vitro titration. Group 3 had the heparin dose titrated, and group 4 had the protamine dose titrated. Coagulation tests, bleeding, and transfusion requirements were measured.

Results

The initial heparin bolus predicted by the titration was < 300 U· kg^?1 in all patients. Group 2 received a lower heparin bolus for the initiation of bypass but total heparin doses were not different among groups (group 1 = 365 ± 43, group 2= 348 ± 73 U · kg^?1, group 3= 394 ± 86 U · kg^?1, group 4= 376 ± 60; P = 0.06). Groups 2 and 4 received a lower initial and a lower total protamine dose (total dose group 1 = 4.03 ± 0.65 mg · kg^?1, group 2 = 3.56 ±1.11 mg · kg^?1, group 3= 4.22 ± 0.90 mg · kg^?1, group 4= 3.38 ± 0.98 mg· kg^?1,P = 0.001). The incidences of incomplete heparin neutralisation (P = 0.14) and heparin rebound (P = 0.1) were not different among groups. Postoperative bleeding and transfusion requirements did not differ.

Conclusion

In cardiac surgical patients, heparin and protamine titration did predict a lower protamine dose but did not result in a measurable improvement in haemostasis during the perioperative period.     

Clevidipine compared with nitroglycerin for blood pressure control in coronary artery bypass grafting: a randomized double-blind study

Purpose

We tested the hypothesis that clevidipine, a rapidly acting dihydropyridine calcium channel blocker, is not inferior to nitroglycerin (NTG) in controlling blood pressure before cardiopulmonary bypass (CPB) during coronary artery bypass grafting (CABG).

Methods

In this double-blind study from October 4, 2003 to April 26, 2004, 100 patients undergoing CABG with CPB were randomized at four centres to receive intravenous infusions of clevidipine (0.2-8 μg·kg^?1·min^?1) or NTG (0.4 μg·kg^?1·min^?1 to a clinician-determined maximum dose rate) from induction of anesthesia through 12 hr postoperatively. The study drug was titrated in the pre-CPB period with the aim of maintaining mean arterial pressure (MAP) within ± 5 mmHg of a clinician-predetermined target. The primary endpoint was the area under the curve (AUC) for the total time each patient’s MAP was outside the target range from drug initiation to the start of CPB, normalized per hour (AUC_MAP-D). The predefined non-inferiority criterion for the primary endpoint was a 95% confidence interval (CI) upper limit no greater than 1.50 for the geometric means ratio between clevidipine and NTG.

Results

Total mean [standard deviation (SD)] dose pre-bypass was 4.5 (4.7) mg for clevidipine and 6.9 (5.4) mg for NTG (P < 0.05). The geometric mean AUC_MAP-D for clevidipine was 283 mmHg·min·hr^?1 (n = 45) and for NTG was 292 mmHg·min·hr^?1 (n = 48); the geometric means ratio was 0.97 (95% CI 0.74 to 1.27). The geometric mean AUC_MAP-D during aortic cannulation was 357.7 mmHg·min·hr^?1 for clevidipine compared with 190.5 mmHg·min·hr^?1 for NTG. Mean (SD) heart rate with clevidipine was 76.0 (13.8) beats·min^?1 compared with 81.5 (14.4) beats·min^?1 for NTG. There were no clinically important differences between groups in adverse events.

Conclusion

During CABG, clevidipine was not inferior to NTG for blood pressure control pre-bypass.     

Smoking increases the requirement for rocuronium

Purpose

To compare the potency of rocuronium in non-smokers and smokers during general anaesthesia.

Methods

In a randomized, open clinical study, 40 patients, 17–62 yr of age, were anaesthetized with propofol, alfentanil and nitrous oxide in oxygen. After obtaining individual dose-response curves for rocuronium, bolus doses of rocuronium were given to maintain neuromuscular block at 90–99% for 60 min. Evoked adductor pollicis electromyography (EMG) was used to monitor neuromuscular block.

Results

The ED₉₅ values (± SEM) for rocuronium were 460.5 ± 28.9 and 471.5 ± 22.1 μg·kg^?1 for nonsmokers and smokers, respectively (P:NS). However, doses of rocuronium to maintain 90–99% neuromuscular block (± SEM) were 620.1 ± 46.7 and 747.4 ± 56.0 μg·kg^?1·hr^?1 for non-smokers and smokers, respectively (P = 0.0504).

Conclusion

The results may indicate increased metabolism of rocuronium in smokers rather than increased requirement of rocuronium at the receptor site.     

Thoracic epidural block attenuates cardiovascular response to apnea in rabbits

Purpose

Apnea is one of the potential complications during anaesthesia. If sympathetic nerve activity is blocked by epidural anaesthesia, circulatory responses to apnea might change. Our objective was to assess the potential modifying effects of epidural anaesthesia on the cardiovascular responses to apnea in the animals.

Methods

Twenty rabbits anaesthetised with pentobarbital (25 mg·kg^?1 iv, 8 mg·kg^?1·hr^?1) and pacuronium bromide (0.2 mg·kg^?1·hr^?1 iv) were randomly assigned to one of two groups: control (n = 10) and epidural (n = 10). In the control group, 0.6 ml saline, and in the epidural group, 0.6 ml lidocaine 1% was injected into the epidural space respectively. After mechanical ventilation with FIO₂ 0.4, apnea was induced by disconnecting the anaesthetic circuit from the endotracheal tube, and mean arterial pressure (MAP), heart rate (HR), and time to cardiac arrest were measured.

Results

Before apnea MAP was lower in the epidural than in the control group (73 ± 10vs 91 ± 10 mmHg,P < 0.05). Heart rate was not different between groups (264 ± 36vs 266 ± 24 bpm). Mean arterial pressure increased in the control group after apnea, but not in the epidural group. The time to cardiac arrest was less in the epidural group than in the control group (420 ± 67vs 520 ± 61 sec,P < 0.05). Heart rate decreased markedly after apnea in the control group whereas it decreased gradually in the epidural group.

Conclusion

Thoracic epidural anaesthesia attenuated cardiovascular response to apnea and reduced the time to cardiac arrest.     

Plasma lipid concentrations correlate inversely with CPB-induced interleukin-6 release

Purpose

Cardiopulmonary bypass (CPB) is characterized by translocation of intestinal endotoxin and subsequent endogenous production of the pro-inflammatory cytokine interleukin-6 (IL-6). Plasma lipid fractions, especially high density lipoproteins, bind and neutralize endotoxin and, therefore, inhibit endotoxin-induced macrophage cytokine production, including IL-6. Increased IL-6 plasma levels have been implicated in adverse consequences associated with CPB. Previous studies demonstrated large interpatient variability in IL-6 plasma levels after CPB. The purpose of this study was to evaluate the relationship between plasma lipid concentrations and the concentrations of IL-6 following CPB in humans.

Methods

In a prospective study, a group of 15 patients selected to exclude variables known to influence post-CPB plasma levels of IL-6 (preoperative left ventricular ejection fraction > 45%, similar durations of aortic cross clamping and total CPB time, similar temperature control during CPB, and avoidance of platelet transfusion and shed mediastinal blood re-infusion), IL-6 was measured at baseline, one and 24 hr post-CPB.

Results

Interleukin-6 plasma concentrations (mean ± SD) increased at one (142 ± 89 pg·ml^?1,P < 0.05) and 24 (129 ± 82 pg·ml^?1,P < 0.05) hr post-CPB compared with baseline (1,5 ± 1 pg·ml^?1) concentrations. An inverse correlation was found between IL-6 plasma concentrations at one hour post-CPB and plasma cholesterol concentrations (r = -0.592,P = 0.02), high density lipoprotein (r = -0.595,P = 0.02), and low density lipoprotein (r = -0.656,P = 0.01).

Conclusions

These results suggest that plasma lipids attenuate the production of IL-6 during CPB and may partly explain the variability of interpatient levels of IL-6 reported post-CPB by others.     

Epidural and intravenous bolus morphine for postoperative analgesia in infants

Purpose

To compare two doses of bolus epidural morphine with bolus iv morphine for postoperative pain after abdominal or genitourinary surgery in infants.

Methods

Eighteen infants were randomly assigned to bolus epidural morphine (0.025 mg · kg^?1 or 0.050 mg · kg^?1) or bolus iv morphine (0.050–0.150 mg · kg^?1). Postoperative pain was assessed and analgesia provided, using a modified infant pain scale. Monitoring included continuous ECG, pulse oximetry, impedance and nasal thermistor pneumography. The CO₂ response curves and serum morphine concentrations were measured postoperatively.

Results

Postoperative analgesia was provided within five minutes by all treatment methods. Epidural groups required fewer morphine doses (3.8 ± 0.8 for low dose [LE], 3.5 ± 0.8 for high dose epidural [HE] vs. 6.7 ± 1.6 for iv, P < 0.05) and less total morphine (0.11 ± 0.04 mg · kg^?1 for LE, 0.16 ± 0.04 for HE vs 0.67 ± 0.34 for iv, P < 0.05) on POD1 Dose changes were necessary in all groups for satisfactory pain scores. Pruritus, apnoea, and haemoglobin desaturation occurred in all groups. CO₂ response curve slopes, similar preoperatively (range 36–41 ml · min^?1 · mmHg ETco ₂ ^?1 · kg^?1) were generally depressed (range, 16–27 ml · min^?1 · mmHg ETco ₂ ^?1 · kg^?1) on POD1. Serum morphine concentrations, negligible in LE (<2 ng · ml^?1), were similar in the HE and iv groups (peak 8.5 ± 12.5 and 8.6 ± 2.4 ng · ml^?1, respectively).

Conclusion

Epidural and iv morphine provide infants effective postoperative analgesia, although side effects are common. Epidural morphine gives satisfactory analgesia with fewer doses (less total morphine); epidural morphine 0.025 mg · kg^?1 is appropriate initially. Infants receiving epidural or iv morphine analgesia postoperatively need close observation in hospital with continuous pulse oximetry.     

Tacrine does not alter the potency of succinylcholine in the rat

Purpose

Tacrine is a cholinesterase inhibitor used to manage Alzheimer’s dementia. Giveniv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known.

Methods

Groups of adult rats were given 2.5 mg · kg^?1 tacrine (chronic groups) or 1 ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg · kg^?1 tacrineiv. Twelve to 18 hr after the last gavage of tacrine or saline, and ~20 min afteriv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation.

Results

The ED₅₀ and ED₉₅ of succinylcholine in control rats were (mean ± SD) 204 ± 41 and 382 ± 96 μg · kg^?1 respectively, in the tibialis muscle, and 280 ± 52 and 629 ± 168 μg · kg^?1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED₅₀ and ED₉₅ ranged from 166–197 and 277–396 μg · kg^?1, respectively, in the tibialis muscle, and 248–333 and 546–667 μg · kg^?1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group.

Conclusion

Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.     

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs

Purpose

To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane.

Methods

Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg·kg^?1 induction dose and 20 mg·kg^?1·hr^t-1 infusion), propofol (5 mg·kg^?1 induction dose and 40 mg·kg^?1·hr^?1 infusion), etomidate (2 mg·kg^?1 induction dose and 5 mg·kg^?1·hr^?1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%.

Results

Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentoneor propofol-than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 ± 19 % during isoflurane alonevs + 182 ± 27 % change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone.

Conclusions

The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.     

RETRACTED ARTICLE: Diltiazem-lidocaine combination for the attenuation of cardiovascular responses to tracheal intubation in hypertensive patients

Purpose

Hypertensive patients are prone to haemodynamic changes after laryngoscopy and tracheal intubation. This study was undertaken to compare the efficacy of a combination of diltiazem and lidocaine with that of each drug alone for suppressing the cardiovascular responses to trachéal intubation.

Methods

Sixty hypertensive patients (ASA II), defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg (World Health Organization), undergoing elective surgery received, in a randomized, double-blind manner, 0.3 mg·kg^?1 diltiazem, 1.5 mg·kg^?1 lidocaine, or 0.3 mg·kg^?1 diltiazem plus 1.5 mg·kg^?1 lidocaineiv (n = 20 of each) before the initiation of laryngoscopy. Anaesthesia was induced with 5 mg·kg^?1 thiopentoneiv, and tracheal intubation was facilitated with 2 mg·kg^?1 succinylcholineiv after precurarization with 0.02 mg·kg^?1 vecuroniumiv. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and at immediate, 1, 2, 3, 5 and 10 min after tracheal intubation.

Results

The inhibitory effects of diltiazem-lidocaine combination on cardiovascular responses to tracheal intubation was greater than those of diltiazem or lidocaine as a sole medicine (RPP; 10602 ± 1448 (combination)vs 11787 ± 1345 (diltiazem), 15428 ± 1756 (lidocaine), mean ± SD,P < 0.05).

Conclusion

Prophylactic therapy with diltiazem-lidocaine combination is more effective than diltiazem or lidocaine alone for attenuating the cardiovascular changes associated with tracheal intubation in hypertensive patients.     

Propofol reduces succinylcholine induced increase of masseter muscle tone

Purpose

Succinylcholine is known to increase the tone of the masseter muscles. As excessive jaw tension may complicate rapid sequence induction, we investigated three induction techniques, all including the use of succinylcholine, with respect to masseter muscle tone, neuromuscular blockade, intubation conditions, and time course of intubation.

Methods

Sixty adult patients were allocated to one of three induction groups: Group THIO received 5 mg · kg^?1 thiopentone, Group THIO/ATR received 5 mg · kg^?1 thiopentone plus 0.05 mg · kg^?1 atracurium for precurarization, and Group PROP received 2.5 mg · kg^?1 propofol. All patients received 3 μg · kg^?1 fentanyl and 1.5 mg · kg^?1 succinylcholine. Time for induction of anaesthesia was recorded, and, after inserting a Grass Force Transducer between upper and lower incisors, jaw tone and the time course of jaw tension was recorded before and after the administration of succinylcholine.

Results

No differences in the onset of sleep were observed among the three groups (Group THIO 33 ± 2 sec: THIO/ATR 30 ± 2 sec: PROP 35± 2 sec, mean ± SE). Masseter preloads following induction of anaesthesia were similar in all three groups (THIO 16.4 ± 2.1 N: THIO/ATR 15.1 ± 2.0 N: PROP 12.7 ± 1.6 N). However, after administration of succinylcholine, the increase in masseter tone was less in Groups PROP (5.0 ±1.1 N) and THIO/ATR (6.4 ± 2.1 N) than in Group THIO (12.4 ± 3.0 N;P < 0.05).

Conclusion

Jaw tension after administration of succinylcholine is influenced by the choice of induction agent. The increase of masseter muscle tone is lower following propofol or thiopentone/atracurium induction than with thiopentone alone.     

Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery

Purpose

To investigate whether ulinastatin pretreatment (6000 U · kg^?1 before CPB and before declamping of aorta) influenced the production of cytokines and adhesion molecules in the peripheral circulation.

Methods

This prospective randomized study was performed in 22 patients undergoing cardiac surgery. They were divided into two groups. Patients in Group I were untreated and in Group II treated with ulinastatin. The soluble intercellular adhesion molecule-1 (S-ICAM-1), soluble endothelial leukocyte adhesion molecule-1 (S-ELAM-1), interleukin8 and 6 (IL-8, 6) were measured using ELISA kits.

Results

Serum S-ICAM-1 concentration in Group I increased from the preoperative value of 297 ± 27 ng · kg^?1 to 418 ± 106 ng · kg^?1 at 60 min after declamping of the aorta (P < 0.01) but did not change in Group II. Serum S-ELAM-1 concentration did not change in either group. Serum concentration of IL-8 and IL-6 in Group I (37 ± 44 pg · kg^?1, and 59 ± 59 pg · kg^?1, preoperatively) increased to 169 ± 86 pg · kg^?1 and 436 ± 143 pg · kg^?1 at 60 min after declamping of the aorta (P < 0.001, P < 0.001). The increases were greater than those from 25 ± 6 pg · kg^?1 and 30 ± 26 pg · kg^?1 to 56 ± 36 pg · kg^?1 and 132 ± 78 pg · kg^?1 in Group II (P < 0.001, P < 0.001). The levels of S-ICAM-1 correlated with those of IL-8 (r = 0.5, P < 0.001).

Conclusion

These results suggest that ulinastatin may suppress the increase in IL-8 production and the expression of ICAM-1 during cardiac surgery.     

Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia

Purpose

To determine the magnitude of the potentiation of rocuronium by desflurane, isoflurane and sevoflurane 1.5 MAC anaesthesia.

Methods

In a prospective, randomised, study in 80 patients, the cumulative dose-effect curves for rocuronium were determined during anaesthesia with desflurane, sevoflurane and isoflurane (with N₂O 70%, 15 min steady state) or total intravenous anaesthesia (TIVA) using propofol/fentanyl. Neuromuscular block was assessed by acceleromyography (TOF-Guard®) after train-of-four (TOF) stimulation of the ulnar nerve (2Hz every 12sec, 200 μsec duration), Rocuronium was administered in increments of 100 μg·kg^?1 until first twitch (T₁) depression > 95%.

Results

Rocuronium led to more pronounced T₁ depression with desflurane or sevoflurane anaesthesia than with TIVA. The ED₅₀ and ED₉₅ were lower during desflurane (95 ± 25 and 190 ± 80 μg·kg^?1) and sevoflurane (120 ±30 and 210 ± 40 μg·kg^?1) than with TIVA (150 ± 40 and 310 ± 90 μg·kg^?1) (P < .01), while the difference was not significant for isoflurane (130 ± 40 and 250 ± 90 μg·kg^?1). Following equi-effective dosing (T₁ > 95%) the duration to 25% T₁ recovery, recovery index (25/75), and TOF_0.70 was: 13.2 ± 1.8, 12.7 ± 3.4, and 26.9 ± 5.7 min during anaesthesia with desflurane; 15.5 ± 5.0, 11.4 ± 3.8, and 31.0 ± 6.0 min with sevoflurane; 13.9 ± 4.7, 10.7 ± 3.3, and 26.3 ± 8.9 min with isoflurane; and 13.9 ± 3.9, 11.3 ± 5.7, and 27.5 ± 8,2 min with TIVA anaesthesia (P: NS).

Conclusion

Interaction of rocuronium and volatile anaesthetics resulted in augmentation of the intensity of neuromuscular block but did not result in significant effects on duration of or recovery from the block.     

Bradycardia produced by pyridostigmine and physostigmine

Purpose

The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists.

Methods

Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M₁ receptors were blocked with hexamethonium and pirenzepine, respectively. M₂ receptors were blocked with gallamine, pancuronium and AFDX-116.

Results

With pyridostigmine and physostigmine, the dose-response relationship for the decrease in heart rate (ED₅₀ 1.05 ± 0.25 and 0.198 ± 0.03 mg·kg^?1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED₅₀ 0.094 ± 0.03 and 0.032 ± 0.01 mg·kg^?1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 ± 0.08 and 0.32 ± 0.08 mg·kg^?1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyndostigmine and physostigmine was blocked by hexamethonium (ED₅₀ 10 ± 1.3 and 15.3 ± 2.4 mg·kg^?1, respectively), pirenzepine (ED₅₀ 68 ± 16 and 138 ± 32 μg·kg^?1. respectively), gallamine (56 ± 11 and 67 ± 17 μg·kg^?1, respectively ), pancuronium (32 ± 10 and 30 ± 4 μg·kg^?1, respectively), and AFDX-116 (31 ± 4 and 28 ± 4 μg·kg^?1, respectively).

Conclusion

The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscannic M₁ and a high sensitivity to muscarinic M₂ receptor antagonists.     

Preoperative ketorolac increases bleeding after tonsillectomy in children

Purpose

To compare the incidence of vomiting following codeine or ketorolac for tonsillectomy in children.

Methods

We had planned to enrol 240 patients, aged 2–12 yr undergoing elective tonsillectomy into a randomized, single-blind study in University Children’s Hospital. The study was terminated, after 64 patients because interim analysis of the data by a blinded non-study scientist concluded that the patients were at undue risk of excessive perioperative bleeding. After induction of anaesthesia by inhalation with N₂O/halothane or with propofol 2.5?3.5 mg· kg^?1 iv, the children were administered 150 μg· kg^?1 ondansetron and 50 μg · kg^?1 midazolam. Maintenance of anaesthesia was with N₂O and halothane in O₂. Subjects were administered either 1.5 mg · kg^?1 codeine im or 1 mg· kg^?1 ketorolac iv before the commencement of surgery. Intraoperative blood loss was measured with a Baxter Medi-Vac® Universal Critical Measurement Unit. Postoperative management of vomiting and pain was standardized. Vomiting was recorded for 24 hr after anaesthesia. Data were compared with ANOVA, Chi-Square analysis and Fisher Exact Test.

Results

Thirty-five subjects received ketorolac. Demographic data were similar. The incidence of vomiting during the postoperative period was 31% in the codeine-group and 40% in the ketorolac-group. Intraoperative blood losses was 1.3 ± 0.8 ml · kg^?1 after codeine and 2.2 ± 1.9 ml · kg^?1 after ketorolac (mean ± SD) P < 0.05. Five ketorolac-treated patients had bleeding which led to unscheduled admission to hospital, P < 0.05, Exact Test.

Conclusion

Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects.     

Optimal dose of thiamylal in combination with midazolam for induction of anaesthesia

Purpose

The optimal dose range of thiamylal, combined with midazolam, in the induction of anaesthesia was evaluated using haemodynamic variables.

Methods

The 200 patients, aged 30 to 70 yr, were randomly divided into five groups by midazolam dosage. Anaesthesia was induced with midazolam 0.05, 0.075, 0.10, 0.15, or 0.20 mg · kg^?1. Two minutes later, 50 mg thiamylal was administered followed by 25 mg increments until verbal response and eyelash reflex disappeared and blood pressure decreased to a level less than that of preinduction. Tracheal intubation was performed with 0.15 mg · kg^?1 vecuronium. Blood pressure and heart rate were monitored during induction. Optimal induction was defined as a systolic blood pressure one minute after intubation within ±20% of that before induction.

Results

There were 164 patients whose systolic blood pressure were within these criteria. Blood pressure decreased two minutes after induction and 3 to 15 min after intubation in all groups. Heart rate increased one minute after intubation in 0.05 mg · kg^?1, 0.075 mg · kg^?1 and 0.10 mg · kg^?1 midazolam groups. The optimal range of thiamylal was 4.0 ± 1.1 (mean + SD), 3.1 ± 1.2, 2.8 ± 1.1, 2.3 ± 1.2, and 1.7 ± 1.0 mg · kg^?1 in combination with midazolam 0.05, 0.075, 0.10, 0.15, and 0.20 mg · kg^?1, respectively.

Conclusion

The optimal dose range, to maintain haemodynamic stability, for thiamylal induction of anaesthesia in combination with midazolam, 0.05-0.2 mg · kg^?1 was found to range from 4.0 to 1.7 mg · kg^?1.     

RETRACTED ARTICLE: Calcium channel blockers attenuate cardiovascular responses to tracheal extubation in hypertensive patients

Purpose

Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to examine the inhibitory effects of calcium channel blockers, nicardipine and diltiazem, on haemodynamic changes after tracheal extubation.

Methods

Sixty hypertensive patients (ASA physical status II) undergoing elective orthopaedic (upper and lower extremity) surgery received, in a randomized, double-blind manner, 30 μg·kg^?1 nicardipine, 0.2 mg·kg^?1 diltiazem or saline (as a control) (n = 20 of each) iv before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation.

Results

The HR, MAP and RPP increased after tracheal extubation in the control group (P < 0.05). The increases in these haemodynamic variables were attenuated with nicardipine or diltiazem. The inhibitory effects of diltiazem on these cardiovascular responses to tracheal extubation were greater than those of nicardipine (HR; 86 ±7vs 101 ± 10, RPP; 1 1437 ± 1575vs 14675 ± 2874, mean ± SD,P < 0.05).

Conclusion

Compared with nicardipine, administration of diltiazem produced greater attenuating the circulatory responses to tracheal extubation in hypertensive patients.     

Postoperative analgesia with “3-in-1” femoral nerve block after prosthetic hip surgery

Purpose

To evaluate the efficacy of a single shot “3-in-1” femoral nerve block for prosthetic hip surgery in association with general anaesthesia on post-operative analgesia.

Methods

Forty patients, ASA 1 to 3, received sham block or “3-in-1” femoral nerve block, following Winnie’s landmarks with a nerve stimulator, and 40 ml bupivacaine 0.5% with epinephrine were injected after induction of anaesthesia. Vecuronium, 0.1 mg· kg^?1, was added after performing the block and anaesthesia was maintained with isoflurane, oxygen 40% and nitrous oxide 60%. Fentanyl, 1.5 μg· kg^?1, was administered before incision to all patients. Heart rate, blood pressure, fentanyl requirements and F_ETiso were measured throughout surgery. During the post-operative period, 75 mg diclofenacim and/or 0.1 mg· kg^?1 morphine sc were administered when pain score was > 3/10 and repeated when necessary. Pain scores at first analgesic intervention, at 24 hr and 48 hr as well as diclofenac and morphine requirements after surgery were recorded.

Results

There was no difference in anaesthetic requirements during surgery. The time from performance of sham or “3-in-1” femoral nerve block to the first analgesic intervention (261 ± 49 min versus 492 ± 40 min,P < 0.05) and time from extubation to the first analgesic intervention (61 ± 44 minvs 298 ± 39 min,P < 0.05) were prolonged in the study group. However, pain scores and the analgesic requirements in the postoperative periods (24 and 48 hr) were similar.

Conclusion

There is a short-term benefit during the first few postoperative hours in using a single shot “3-in-1” femoral nerve block to complement general anaesthesia for elective hip surgery.     

Midazolam reverses histamine-induced bronchoconstriction in dogs

Purpose

Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway.

Methods

After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg · kg^?1 pentobarbitoneiv, and were paralysed with 200 μg · kg^?1 · hr^?1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the nght bronchus. A videopnnter printed the BCA which was then measured with a NIH Image program. Bronchoconstnction was produced with histamine (H) 10 μg · kg^?1 followed by 500 μg · kg^?1 · hr^?1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg · kg^?1 midazolam and 25 μg · kg^?1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazeniliv. At the same time, arterial blood was sampled for plasma catecholamine measurement.

Results

Histamine infusion decreased BCA to 49.7 ± 17.3% of basal BCA More than 0.1 mg · kg^?1 midazolam increased BCA up to 71.7 ± 15.3% of the basal (1.0 mg · kg^?1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 ± 3.8 to 3.7 ± 1.9 ng · ml^?1 by 1.0 mg · kg^?1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release.

Conclusion

Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.