Effets de l’halothane sur les gaz du sang et l’équilibre acido-basique artériels chez le rat intact et chez le rat chémodénervé

L’halothane diminue la réponse ventilatoire à l’hypoxie et l’activité des chémorécepteurs artériels périphériques, réalisant une «chémodénervation chimique». Afin d’évaluer le rôle de cette «chémodénervation chimique» dans les modifications de l’équilibre acido-basique et des gaz du sang artériel provoquées par l’halothane, ces paramètres ont été mesurés chez des rats intacts éveillés, puis anesthésiés, et chez des rats chémodénervés, éveillés puis anesthésiés. Le niveau de l’anesthésie pouvant être modifié par la chémodénervation anatomique, l’ED₅₀ inspirée d’halothane a été mesurée chez six rats avant et après chémodénervation anatomique. D’éventuelles modifications hémodynamiques dues à l’halothane et /ou à la chémodénervation anatomique pouvant interférer avec les résultats, la pression artérielle systémique et la fréquence cardiaque ont été mesurées chez six rats intacts éveillés, puis anesthésiés, et chez les six mêmes rats chémodénervés, éveillés puis anesthésiés. Chez neuf rats intacts et chez 19 rats chémodénervés, le pH artériel, la concentration artérielle de bicarbonates, et les gaz du sang artériel (PaO₂ et PaCO₂) ont été mesurés avant et après administration d’halothane. La chémodénervation anatomique ne modifia ni l’ED₅₀ inspirée (1,1%), ni la pression artérielle moyenne et la fréquence cardiaque. Les effets hémodynamiques de l’halothane furent comparables chez les rats intacts et chez les rats chémodénervés. Les modifications des gaz du sang et de l’équilibre acido-basique provoquees par l’halothane chez les rats intacts, et par la chémodénervation anatomique chez les rats éveillés, ne furent pas significativement différentes: diminution significative de PaO₂ et de pHa, augmentation significative de PaCO₂ Chez les rats chémodénervés, l’halothane provoqua une diminution supplémental de PaO₂ et une augmentation supplémentaire de PaCO₂. Le fait que l’halothane et que la chémodénervation anatomique modifient de la même manière les gaz du sang et l’équilibre acido-basique est en faveur de l’action «chémodénervatrice chimique» de l’halothane. Mais les effets additionnels de l’halothane chez l’animal chémodénervé anatomiquement confirment que les effets de l’halothane sur les gaz du sang et l’équilibre acido-basique résultent de multiples points d’impact sur le système respiratoire.     

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T₄/T₁ > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-offour (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg · kg^?1, during thiopentone-N₂O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg · kg^?1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg · kg^?1, was given. Two minutes later, edrophonium, 0.1 mg · kg^?1, was given if T₄/T₁ did not reach 0.7. After another two minutes, edrophonium, 0.2 mg · kg^?1, was given if T₄/T₁ did not reach 0.7 or more. Finally, if T₄/ T₁ was still < 0.7, a dose of 0.4 mg · kg^?1 was given. Seventeen patients (42.5%) required 0.1 mg · kg^?1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg · kg^?1 and six patients (15%) required 0.4 mg · kg^?1. Only one patient received 0.8 mg · kg^?1. There was a good correlation between T₄/ T₁ two minutes after the first dose of edrophonium and pre-reversal T₄/T₁ (r = 0.6; P = 0.00014). All patients with pre-reversal T₄/ T₁ > 0.23 required at most 0.2 mg · kg^?1 of edrophonium for successful reversal. We conclude that when all four twitches are clearly visible following train-of-four stimulation, small doses of edrophonium (0.1-0.2 mg · kg^?1) might be sufficient to antagonize vecuronium neuromuscular blockade.     

Bolus doses of esmolol for the prevention of perioperative hyper-tension and tachycardia

The effectiveness of esmolol, an ultra short-acting cardioselective beta blocker, in the prevention and treatment of post-intubation haemodynamic perturbations, was investigated. Forty-eight ASA physical status I and II patients undergoing hysterectomy were randomly assigned to receive a single intravenous bolus of placebo, esmolol 100 mg, or esmolol 200 mg in a double-blind fashion. This was administered over 15 sec, and immediately followed by thiopentone 3-5 mg.kg-1, succinylcholine 1.5 mg.kg-1, and tracheal intubation 90 sec later. The heart rate following induction of anaesthesia was lower in the esmolol 200 mg group (P less than 0.01); following intubation, the increase in heart rate in the placebo group was greater than in the esmolol groups (P less than 0.05). The systolic blood pressure post-induction was lower in the esmolol 200 mg group (P less than 0.05); following intubation, however, no significant differences were seen among groups in systolic, diastolic, or mean blood pressures. Following tracheal intubation, the incidence of ventricular arrhythmias was lower in the esmolol groups (P less than 0.05). In summary, esmolol in 100 mg and 200 mg doses was effective in mitigating the haemodynamic response following tracheal intubation.     

A clinical comparison of indices of pulmonary gas exchange with changes in the inspired oxygen concentration

Several indices have been introduced as convenient alternatives to calculation of the physiological shunt fraction (Qs/QT) for the assessment of pulmonary gas exchange. These include: the arterial-alveolar oxygen tension ratio (a/APO2), the arterial oxygen tension-inspired oxygen concentration ratio (PaO2/FIO2), the respiratory index (RI), [A-a)DO2/PaO2) and the alveolar-arterial oxygen tension difference [A-a)Do2). These indices are in use clinically despite the fact that they may not accurately predict gas exchange in situations where FIO2, Qs/QT or arterial-venous oxygen content is changing. The clinical stability of each of these indices, relative to the behaviour of the physiological shunt, was therefore investigated prospectively in ten mechanically ventilated postoperative adults as FIO2 was varied from 0.30 to 1.00. None of the indices studied reliably reflected the behaviour of the physiological shunt. As FIO2 was increased incrementally from 0.30 to 1.00, 42 to 55 per cent of the measured changes in these indices were opposite in direction to the corresponding changes in the physiological shunt. The maximum magnitudes of the opposite changes were substantial; 24 and 22 per cent for the a/APO2 and PaO2/FIO2 ratio respectively, 67 per cent for the RI and 101 per cent for the (A-a)DO2. We conclude that the use of any of these indices for clinical assessment of a patient's gas exchange defect when FIO2 is varying can be substantially misleading.     

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).     

Low-dose sufentanil and lidocaine supplementation of general anaesthesia

This randomized double-blind study compared the effects of: (1) saline infusion (C); (2) sufentanil alone (1.0 micrograms.kg-1) (S); and (3) low-dose sufentanil (0.5 micrograms.kg-1) in combination with lidocaine (1.5 mg.kg-1) (LS): on the cardiovascular responses to tracheal intubation and on postoperative ventilation as monitored by respiratory inductive plethysmography in day-care surgical procedures of approximately 60 min duration. Thirty healthy, unpremedicated patients were studied. Thiopentone requirements were reduced by 40 and 28 per cent in the S and LS groups respectively compared with control (P less than 0.001). Both treatments suppressed HR and BP responses (P less than 0.005) to intubation. Postoperatively, PaCO2 was elevated (P less than 0.05) in group S. Dose-related respiratory depression was observed. The incidence of postoperative apnoea was significantly higher in both S and LS groups than compared with control (P less than 0.05). However, only patients in group S showed higher apnoea index and mean apnoea duration over the initial 10-20 min after surgery compared with control (P less than 0.005). In addition, group S showed slower respiratory frequency and prolonged expiratory time (P less than 0.005). In conclusion, an induction dose of sufentanil (1 microgram.kg-1) used in balanced anaesthesia of less than 70 min duration was associated with significant respiratory depression, particularly during the initial 10-20 min after surgery, whereas low-dose sufentanil (0.5 micrograms.kg-1) with lidocaine (1.5 mg.kg-1) had minimal postoperative respiratory depression and comparable attenuation of pressor responses to intubation.     

Intraoperative anaphylaxis to latex

This case report describes intraoperative anaphylaxis occurring in a fourteen-year-old female with spina bifida in which latex surgical gloves were incriminated as the aetiologic agent. The patient was non-atopic but since eight years of age she had developed localized angioedema and urticarial skin reactions on exposure to rubber. She had previously undergone several uneventful surgical procedures. Forty-five minutes following induction of anaesthesia and during laparotomy for elective cholecystectomy she experienced sudden onset of increased airway pressure, oxygen desaturation, tachycardia, profound hypotension and erythema consistent with an anaphylactic reaction. Resuscitation with manual ventilation and oxygen, intravenous fluids and an epinephrine infusion was successful. Subsequent investigations for allergies demonstrated a strongly positive skin prick test and RAST to latex antigen, with negative results to anaesthetic agents, antibiotics and inhalant allergens. During two later operations prophylaxis consisting of diphenhydramine, ranitidine and hydrocortisone appeared to prevent further reactions. Latex should be considered as a cause of life-threatening intraoperative allergic reactions in patients with a history of rubber allergy or frequent exposure to latex products.     

Intraoperative awareness due to malfunction of a Siemens 900B ventilator

A case of intraoperative awareness during a thoracotomy is described. The patient's recall coincided with an intraoperative period during which a Siemens 900B ventilator and a Siemens 952 isoflurane vaporiser were used. Subsequent assessment of this equipment with an anaesthetic agent analyzer revealed that, at the ventilator settings which had been used, the delivered anaesthetic vapour concentration varied greatly from the vaporizer settings. This problem eventually was traced to a malfunctioning inlet control valve on the ventilator. This complication may have been prevented if the end-tidal anaesthetic concentration had been monitored intraoperatively.     

Behavioral effects of MK-801 in the rat

Several experiments were conducted to study the effects of the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on learning and memory in the rat. Rats displayed impaired performance on several sensorimotor tests and appeared grossly intoxicated when treated IP with 0.2 mg/kg MK-801, but not when treated with lower doses (0.05 or 0.1 mg/kg). Postacquisition performance on two spatial learning tasks involving working memory protocols (reinforced alternation and radial arm maze) was impaired by MK-801 at intoxicating doses (0.2 mg/kg) but not at lower doses (0.05 or 0.1 mg/kg). Using a position habit reversal task, we found that rats could learn to reverse a position habit while under the influence of a nonintoxicating dose of MK-801 (0.1 mg/kg), but when tested on the following day performed as if they did not recall what they had learned. Thus, acute administration of a nonintoxicating dose of MK-801 disrupts the retention of new information learned under the influence of the drug but does not interfere with the performance of tasks that are well learned before the drug is administered. Whether the performance deficits on the spatial learning tasks observed only following intoxicating doses of MK-801 reflect an effect on memory is not clear.     

Efficacy of various dithiol compounds in acute As2O3 poisoning in mice

The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As₂O₃ toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As₂O₃. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD₅₀ of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As₂O₃ poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As₂O₃ (containing a tracer dose of⁷⁴As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated.