Adrenocorticotrophic hormone,cortisol and catecholamine concentrations during insulin hypoglycaemia in dogs anaesthetized with thiopentone

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms. Increases in plasma concentrations of various glucose-raising hormones such as glucagon, catecholamines, adrenocorticotrophic hormone (ACTH), and cortisol are observed under certain conditions associated with stress (haemorrhage and hypoglycaemia). The purpose of this study was to determine the effect of thiopentone anaesthesia on the cathecholamine, ACTH and cortisol response to insulin hypoglycaemia in dogs. Blood sugar (BS), plasma cathecholamine, and ACTH, and serum cortisol concentrations were measured during the course of (1) an intravenous insulin test (ITT) and (2) an ACTH test in conscious and in anaesthetized fasted dogs. During the ITT, the anaesthetized dogs showed a moderate resistance, compared with conscious dogs, to the hypoglycaemic action induced by insulin (blood sugar concentration 30 min after insulin injection: 2.91 ± 0.25 vs 1.93 ± 0.12 mM · L^?1; P < 0.01). In addition, decreased epinephrine (220 ± 27 vs 332 ± 32 pg · ml^?1 ACTH (65 ± 6 vs 90 ± 5 pg · ml^?1) and cortisol (4.48 ± 0.3 vs 6.25 ± 0.5 μg · ml^?1) concentrations were detected 60 min after insulin injection (P < 0.01). The norepinephrine response to hypoglycaemia was not altered by anaesthesia (273 ± 33 vs 325 ± 25 pg · ml^?1). Anaesthetized dogs showed a decreased cortisol response to ACTH at 45 min (5.68 ± 0.54 vs 8.87 ± 0.47 μg · ml^?1) when compared with control dogs (P < 0.001). Haemodynamic variables during anaesthesia showed little changes (P < NS); while respiratory rate was altered (P < 0.01 between 60 and 105 min). Arterial pH was decreased (7.29 ± 0.03 vs 7.36 ± 0.04; P < 0.05) and PaCO₂ was increased (6.8 ± 0.3 vs 5.2 ± 0.3; P < 0.01) at 30 min from induction of anaesthesia but little change was seen after the beginning of the ITT and ACTH tests. We conclude that thiopentone anaesthesia provokes a moderate resistance to the hypoglycaemic action of insulin. This does not appear to be related to increases in plasma concentrations of cathecholamines, cortisol or ACTH. Since the hyperglycaemic effects of cathecholamines and glucagon are synergistic it is possible that glucagon plays an important role in the altered blood sugar response to insulin administration.     

RETRACTED ARTICLE: Effects of calcium channel blockers on circulatory response to tracheal intubation in hypertensive patients: nicardipine versus diltiazem

We studied the circulatory responses to laryngoscopy and tracheal intubation in 37 hypertensive patients who received nicardipine 30 μg · kg^?1 iv (Group N, n = 12), diltiazem 0.3 mg · kg^?1 (Group D, n = 12) or saline placebo (Group C, n = 13) 60 sec before the initiation of laryngoscopy. Anaesthesia was induced with thiopentone 5 mg · kg^?1 iv, and succinylcholine 2 mg · kg^?1 iv was used to facilitate tracheal intubation after precurarization with vecuronium 0.02 mg · kg^?1 iv. In patients in Group C heart rate (HR) increased from 79 ± 14 (baseline) to 110 ± 12 (P < 0.05) associated with tracheal intubation; mean arterial pressure (MAP) increased from 116 ± 8 to 140 ± 77 (P < 0.05) and rate-pressure product (RPP) increased from 13385 ± 2393 to 21251 ± 3883 (P < 0.05). The changes from baseline values in HR and RPP after tracheal intubation in Group D were less than those in Groups C and N (P < 0.05). The increase in MAP following tracheal intubation in Groups N and D was lower than that in Group C (P < 0.05). We conclude that, compared with nicardipine, administration of diltiazem iv is associated with less circulatory response to tracheal intubation in hypertensive patients.     

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.     

Bovine haemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs

Purpose

This study compares the effects of stored red cells, freshly donated blood and ultrapurified polymerized bovine haemoglobin (HBOC) on haemodynamic variables, oxygen transport capacity and muscular tissue oxygenation after acute and almost complete isovolaemic haemodilution in a canine model.

Methods

Following randomization to one of three groups, 24 anaesthetized Foxhounds underwent isovolaemic haemodilution with 6% hetastarch to haematocrit levels of 20%, 15% and 10% before they received isovolaemic stepwise augmentation of 1 g · dl^?1 haemoglobin. In Group 1, animals were given autologous stored red cells which they had donated three weeks before. In Group 2, animals received freshly donated blood harvested during haemodilution. In Group 3, animals were infused with HBOC. Skeletal muscle tissue oxygen tension was measured with a polarographic 12 μ needle probe.

Results

In all groups, heart rate and cardiac index were increased with decreasing vascular resistance during haemodilution (P < 0.05). Haemodynamic variables showed a reversed trend during transfusion when compared to haemodilution but remained below baseline (P < 0.05). Arterial and venous oxygen content were changed in parallel to changes of haematocrit and haemoglobin concentrations but were lower in Group 3 than in Groups 1 and 2 (P < 0.05) during transfusion. In contrast, the oxygen extraction ratio was higher in Group 3 (59 ± 8%, P < 0.01) at the end of transfusion than in Group 1 (37 ± 13%) and 2 (32 ± 5%). In Group 3, mean tissue oxygen tension increased from 16 ± 5 mmHg after haemodilution to 56 ± 11 mmHg after transfusion (P < 0.01) and was higher than in Group 1 (41 ± 9, P < 0.01) and Group 2 (29 ± 11, P < 0.01). While in Group 3 an augmentation of 0.7 g · dl^?1 haemoglobin resulted in restoring baseline tissue oxygenation, higher doses of 2.7 g · dl^?1 and 2.1 g · dl^?1 were needed in Groups 1 and 2 to reach this level (P < 0.01).

Conclusion

The results show a higher oxygenation potential of HBOC than with autologous stored red cells because of a more pronounced oxygen extraction.     

Effect of phenylephrine on histamine-induced bronchoconstriction in dogs

Purpose Although an α-adrenoceptor has been suggested to be involved in the mechanism of asthma, the effect of α₁-agonist on the airway is still unclear. In this study we evaluated the effect of phenylephrine on the airway with a direct visualization method using a superfine fiberoptic bronchoscope (SFB). Methods Seven mongrel dogs were anesthetized with pentobarbital (30 mg·kg⁻¹ IV) and paralyzed by pancuronium (0.2mg·kg⁻¹·h⁻¹). The trachea was intubated with an endotracheal tube (ID 7 mm) that has a second lumen for insertion of a SFB (OD 2.2 mm) to monitor the bronchial cross-sectional area (BCA) continuously. The tip of a SFB was placed at the level between the second and third bronchial bifurcation. To assess hemodynamics, the direct arterial blood pressure (ABP) and pulmonary arterial pressure (PAP) were monitored via a femoral arterial catheter and Swan-Granz catheter. Bronchoconstriction was elicited by histamine (10 μg·kg⁻¹+ 500 μg·kg⁻¹·h⁻¹_. At 30 min after the histamine was started, saline or phenylephrine (1, 10, and 100μg·kg⁻¹) was given intravenously. The BCA and hemodynamic variables were assessed before (basal) and 30 min after the histamine was started and 5 min after saline and each phenylephrine dose. Results Histamine reduced BCA by 40.3±6.3%. Phenylephrine at 10 and 100 μg·kg⁻¹ significantly increased the ABP and PAP; and it significantly decreased the BCA, by 6.5±6.9% and 14.2±7.9%, respectively. Plasma epinephrine and norepinephrine were also significantly reduced following phenylephrine 100 μg·kg⁻¹ IV. Conclusion The dose of phenylephrine that produced vasopressive actions worsened the histamine-induced bronchoconstriction slightly but significantly. Therefore, phenylephrine should be used with caution in asthmatic patients.     

Haemodynamic changes during induced hypotension — comparison of trimethaphan with prostaglandin E1 assessed using transoesophageal echocardiography

Haemodynamic changes during induced hypotension depend upon the hypotensive agent used. We investigated if, using transoesophageal echocardiography (TEE), we could identify the haemodynamic differences between trimethaphan and prostaglandin E₁. Twenty-nine patients undergoing total hip replacement were selected for study. Hypotension was induced to a mean arterial pressure of 8.0– 9.3 kPa with either trimethaphan (5–20 μg · kg^?1 min^?1) or prostaglandin E₁ (0.5–2.0 μg · kg^?1 min^?1). The left atrial dimension, cardiac output, fractional shortening, pulmonary venous flow and mitral valve flow were evaluated using TEE. During induced hypotension, left atrial dimension decreased in both trimethaphan and prostaglandin E₁ groups (P < 0.05). In the trimethaphan-treated patients systolic velocity in pulmonary venous flow decreased from 41.9 ± 4.8 cm · sec^?1 before induced hypotension to 27.8 ± 4.2 cm · sec^?1 by 30 min after stable hypotension had been established (P < 0.01). The late/early ratio of peak velocity in mitral blood flow decreased in prostaglandin E₁ treated patients. Cardiac output increased from 4.2 ± 0.5 L · min^?1 to 5.3 ± 0.4 L · min^?1 during 30 min hypotension with prostaglandin E₁ administration (P < 0.05), but cardiac output decreased from 5.0 ± 0.5 to 3.5 ± 0.4 L · min^?1 with trimethaphan (P < 0.01). The differences in haemodynamic variables could be attributed to the venule dilatation effect of trimethaphan. We conclude that it was possible to detect the haemodynamic differences between trimethephan and prostaglandin E₁ using TEE.     

Haemodynamic,diuretic and hormonal responses to prostaglandin E1, infusion in halothane anaesthetized dogs: comparison among epidural lidocaine,epidural fentanyl and epidural saline

Deliberate hypotension decreases blood loss and transfusion but it may be accompanied by adverse effects due either to the hypotensive agents themselves or to haemodynamic alterations. Prostaglandin E₁ (PGE₁) has the advantage of a diuretic effect coupled with systemic hypotension. To elucidate the mechanisms by which PGE₁ induces diuresis we compared the haemodynamic, diuretic and hormonal responses to PGE₁ infusion simultaneously with epidural lidocaine (EP-L n = 7), epidural fentanyl (EP-F n = 8) or epidural saline (CONT n = 7) in halothane anaesthetized mongrel dogs. All groups developed a decrease in mean arterial pressure during PGE₁ infusion (from 105 ± 24 to 77 ± 18 mmHg in EP-L; 106 ± 19 to 79 ± 13 mmHg in the EP-F; and 129 ± 14 to 106 ± 18 mmHg in the CONT groups (mean ± SD)) (P < 0.05). In the EP-F and CONT groups urinary output increased during PGE₁ infusion (from 4.31 ± 1.89 to 6.15 ± 2.03 ml · min^?1 and 2.71 ± 1.23 to 4.48 ± 1.66 ml · min^?1 (P < 0.05), respectively) and was accompanied by increases in renal blood flow (from 87.0 ± 40.7 to 111.0 ± 42.8 ml · min^?1 and from 121.6 ± 46.6 to 158.4 ± 64.9 ml · min^?1 (P < 0.05), respectively) and in fractional excretion of sodium (FE_Na) (from 4.78 ± 3.88 to 7.63 ± 5.20% in CONT group). Plasma epinephrine concentration increased after laparotomy in the CONT group (from 0.09 ± 0.08 to 0.17 ± 0.14 pg · min^?1) (P < 0.05) and antidiuretic hormone (ADH) concentration increased after laparotomy (from 6.9 ± 5.2 to 21.0 ± 13.0 pg · ml^?1 in EP-F and from 8.1 ± 6.2 to 45.8 ± 29.9 pg · ml^?1 in CONT groups). Plasma renin activity increased after laparotomy in the EP-L group (from 2.00 ± 1.37 to 4.72 ± 2.73 mg · ml^?1 hr^?1) (P < 0.05). The results suggest that the mechansim of the PGE_1? induced diuretic effect includes increases in renal blood flow while renal sympathetic innervation is maintained and in FE_Na in the presence of elevated plasma ADH concentration.     

A comparison of pipecuronium with pancuronium on haemodynamic variables and plasma catecholamines in coronary artery bypass patients

Pipecuronium bromide, a new neuromuscular relaxant with steroidal structure, is devoid of effects on the autonomic nervous system and may be useful in patients where haemodynamic stability is mandatory. However, tracheal intubation may alter this haemodynamic profile. Therefore, we carried out a prospective double-blind study in 30 patients undergoing coronary artery bypass surgery with the purpose (1) of determining if intubation influenced the haemodynamic stability in patients paralyzed with pipecuronium and (2) of comparing plasma catecholamine concentrations after pipecuronium with those after pancuronium. Thirty patients were randomized into two groups receiving either pipecuronium 100 μg·kg^?1 or pancuronium 150 μg·kg^?1 after induction of anaesthesia with midazolam and fentanyl. Haemodynamic variables and plasma catecholamines were measured before and after induction, after the muscle relaxant three times and twice after intubation. After anaesthesia induction decreases in heart rate (HR), mean arterial pressure (MAP) and cardiac index (CI) were observed in both groups. These haemodynamic variables were unchanged after pipecuronium whereas after pancuronium HR increased from 53 ± 11 b · min^?1 to 64 ± 9 b · min^?1 after induction (P < 0.05) and CI from 2.5 ± 0.5 L · min^?1 to 3.0 ± 0.8 L · min^?1 (P < 0.05). Furthermore ECG signs of myocardial ischaemia appeared in four patients after pancuronium and the decay of plasma norepinephrine concentration was slower than with pipecuronium. We conclude that pipecuronium given after induction of anaesthesia is free of sympathomimetic or vagolytic activity and does not influence haemodynamic variables for up to ten minutes after tracheal intubation.     

Dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block during N2O-enflurane-alfentanil anaesthesia

The purpose of this study was to determine the dose-response relationships for edrophonium antagonism of mivacuriuminduced neuromuscular block. Seventy-five ASA I or II adults were given mivacurium 0.15 mg · kg^{? 1} followed by an infusion (7 μg · kg^{? 1} · min^{? 1}) during alfentanil-propofol-N₂O-enflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 20 sec and the response of the adductor pollicis was recorded (Relaxograph NMT-100. Datex, Helsinki, Finland). Mivacurium infusion was modified at five-minute intervals in order to keep the height of the first twitch in TOF (T₁) at 5% of its control value. At the end of surgery, edrophonium (0.0. 0.125, 0.25, 0.5. or 1.0 mg · kg^{? 1}) combined with glycopyrrolate (0.0, 0.0012, 0.0025, 0.005, or 0.01 mg · kg^{? 1}) were administered by random allocation. Edrophonium doses of 0.25, 0.5 and 1.0 mg · kg^{? 1} were different from placebo with regard to time to attain a TOF ratio (fourth twitch in TOF/ T,) = 0.7 (13.8 ± 4.5, 11.1 ± 3.5, 11.4 ± 3.0 vs 19.7 ± 4.7 min P < 0.05). Doses of 0.5 and 1.0 mg · kg^{? 1} permitted faster recovery time of T₁ from 10 to 95% (T_{10– 95}) than did placebo (7.5 ± 3.8,8.9 ± 3.5 vs 14.5 ± 5.0 min P < 0.05). Edrophonium 0.5 mg · kg^{? 1} was different from placebo with regard to recovery time of T₁ from 25 to 75% (T_{25– 75}) (3.3 ± 2.0 vs 6.7 ± 2.0 min P < 0.05). Only edrophonium 0.5 mg · kg^{? 1} provided faster recovery than placebo with regard to all three indices. It is concluded that edrophonium 0.5 + glycopyrrolate 0.005 mg · kg^{? 1} allow the fastest recovery from a mivacurium-induced block during enflurane-N₂O anaesthesia.     

Changes inPetCO2 and pulmonary blood flow after bronchial occlusion in dogs

The use ofPetCO₂ in detecting accidental bronchial intubation was investigated. ThePetCO₂ was measured in six mongrel dogs after occluding the left mainstem bronchus in three conditions; pentobarbital anaesthesia, 0.8% halothane insufflation together withpentobarbital anaesthesia, and simultaneous left pulmonary artery and bronchial airway occlusion with intravenous pentobarbital anaesthesia. An external flow probe measured left pulmonary artery blood flow. ThePetCO₂ decreased after bronchial occlusion during pentobarbital (35 ± 3 vs 30 ± 5 mmHg) and halothane-pentobarbital (30 ± 6 vs 25 ± 6 mmHg) conditions (P < 0.05). However, within three minutes of bronchial occlusion, the values ofPetCO₂ had returned to their pre-occlusion values. After five minutes of bronchial occlusion pulmonary artery blood flow in the non-ventilated lung decreased (P < 0.05) during pentobarbital (770 ± 533 ml · min^?1 vs 575 ± 306 ml · min^?1) and halothane-pentobarbital (495 ± 127 ml · min^?1 vs 387 ± 178ml · min^?1) conditions. Simultaneous bronchial and pulmonary artery occlusion prevented any changes inPetCO₂. It was concluded that accidental one- lung ventilation results in small and transient decreases inPetCO₂. A redistribution of blood flow from the nonventilated to ventilated lung occurs which restoresPetCO₂ to the original values observed with twolung ventilation.     

High-dose vecuronium neuromuscular block: a comparison of arrhythmias and onset of block during sufentanil anaesthesia

This study compared the heamodynamic effects of sufentanil with those observed following concomitant sufentanil and highdose vecuronium administration to determine whether vecuronium induces bradyarrhythmias. Sixty coronary artery bypass patients were stratified into beta blocker (n = 30) or non-beta blocker (n = 30) groups and following induction with sufentanil (9 ± 3 μg · kg^?1) and midazolam (0.07 ± 0.04 mg · kg^?1), received either succinylcholine 1 mg · kg^?1 (SxCh), vecuronium 0.3 mg · kg^?1 (Vec 0.3), or vecuronium 0.5 mg · kg^?1 (Vec 0.5). Using a Holter ECG monitor, bradyarrhythmias were classified as mild (HR 46–50), moderate (HR 40–45) or severe (HR < 40). In the pre-induction period, there were no differences in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups, in either the beta blocker or non-beta blocker groups. Following induction, there were similar reductions in mean heart rate and mean arterial pressure in all three muscle relaxant groups in both the beta and the non-beta blocker groups; however, there was no difference in the incidence of mild, moderate or severe bradyarrhythmias among the SxCh, Vec 0.3 or Vec 0.5 groups. The Vec 0.5 beta blocker group had a higher incidence of mild bradyarrhythmias (32 ± 36%) than the Vec 0.5 non-beta blocker group (2 ± 3% P = 0.017). Using EMG recording, the onset time of maximal neuromuscular block for the Vec 0.3 group (108 ± 17 sec) was longer (P < 0.05) than the SxCh (76 ±21 sec) and Vec 0.5 (82 ± 13 sec) groups, which were similar. We conclude: (i) vecuronium does not affect HR or the incidence of bradyarrhythmias following sufentanil administration and that the observed reduction in HR and mean arterial pressure were due to sufentanil administration, (ii) vecuronium (0.5 mg · kg^?1) provides an onset time of neuromuscular block similar to SxCh, and (iii) patients taking beta blockers preoperatively are more prone to develop bradyarrhythmias during sufentanil administration.     

Neostigmine decreases heart rate in heart transplant patients

Purpose

This study evaluated the effect of neostigmine on heart rate in cardiac transplant patients.

Methods

Neostigmine (2.5–50 μg · kg^?1) was administered to ASA 1 or 2 patients with normally innervated hearts (controls), and to patients who had undergone recent (<six months before study) or remote (> six months before study) cardiac transplantation.

Results

Baseline heart rate was 66 ± 3 beats · min^?1 in controls (n = 10, mean ± SEM), which was slower than that observed in recently (95 ± 4 beats · min^?1, n = 15, P < 0.001) and in remotely (88 ± 3 beats · min^?1, n = 16, P < 0.001) transplanted patients. Neostigmine produced a dose-dependent decrease in heart rate in all patients. Controls were the most sensitive to neostigmine, with a 10% decrease in heart rate produced by an estimated dose of 5.0 ± 1.0 μg · kg^?1. The recently transplanted group was the least sensitive, with the maximum dose producing only an 8.3 ± 0.9% reduction. The response to neostigmine of the remotely transplanted patients was variable. The estimated dose to produce a 10% decrease in heart rate in this group was 24 ± 6 μg · kg^?1 which was greater than that for controls (P = 0.008). Administration of atropine (1.2 mg) reversed the neostigmine-induced bradycardia in all three groups. Reversal of the bradycardia consisted of a transient peak increase in heart rate in controls to 145 ± 6% of baseline, a value which was greater than that observed in recent (103 ± 1%, P < 0.001) and in remote (109 ± 3%, P < 0.001) transplants.

Conclusions

Neostigmine produces a dose-dependent brady-cardia in heart transplant patients. Some remotely transplanted patients may be particularly sensitive to the bradycardic effects of neostigmine.     

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-2O anesthesia

Purpose. Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. Methods. Thirty-six adult patients were randomly assigned to two groups (n = 18 each): the propofol group patients were anesthetized with propofol (5–10 mg·kg⁻¹·h⁻¹)-₂O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%–1.0%)-₂O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg·kg⁻¹ and atropine 0.02 mg·kg⁻¹ was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. Results. At the completion of the surgery, the average infusion rate of propofol was 6.2 ± 1.7 mg·kg⁻¹·h⁻¹, and the average inspired concentration of isoflurane was 0.73 ± 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 ± 9 and 34 ± 6 beats·min⁻¹, respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (−9 ± 4 and −5 ± 4 beats·min⁻¹, respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats·min⁻¹) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). Conclusion. We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia. Received: May 21, 2001 / Accepted: August 29, 2001     

Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg⁻¹·min⁻¹ increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg⁻¹·min⁻¹ showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg⁻¹·min⁻¹, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.     

Stress hormone responses to major intra-abdominal surgery during and immediately after sevoflurane-nitrous oxide anaesthesia in elderly patients

We studied the responses of plasma epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), cortisol, and antidiuretic hormone (ADH) during and immediately after sevoflurane-nitrous oxide anaesthesia supplemented with vecuronium in seven elderly patients (mean 76.6 ± 1.7 SEM) who underwent major intra-abdominal surgery. The plasma concentrations of norepinephrine, ACTH, cortisol, and ADH increased in response to surgical procedures (P <0.05). The plasma concentration of ADH increased to a peak concentration of 189.1 ± 20.7 pg · ml^?1 30 min after skin incision (P < 0.05). the plasma concentrations of epinephrine, norepinephrine, ACTH, and cortisol increased to peak concentrations of 408.6 ± 135.5 pg · ml^?1, 635.7 ± 167.8 pg · ml^?1, 222.6 ± 48.0 pg · ml^?1, and 113.6 ± 67.5 μg · dI^?1, respectively immediately after tracheal extubation (P <0.05). We conclude that, in the elderly patients, the responses of stress hormones to major intraabdominal surgery were preserved during sevoflurane-nitrous oxide anaesthesia sufficient to prevent increases in arterial pressure and heart rate. The strongest responses of epinephrine, norepinephrine, ACTH, and cortisol were elicited immediately after treacheal extubation.     

Augmented sensitivity to benzodiazepine in septic shock rats

The purpose of this study was to assess the pharmacological characteristics of the benzodiazepine binding site in the brain of septic animals. We induced endotoxin shock in rats using a caecum ligation and puncture model. Following examination of the physiological state of the rats 24 hr after the caecum ligation and puncture, brain tissue samples were prepared for biochemical assay of amino acids and for the [³H]-diazepam radioligand binding assay. Amino acids assays indicated that the concentration of aromatic amino acids was higher in the CLP group (P < 0.05), the branched chain amino acid concentration was lower in the CLP group (P < 0.05) and the sulfur-containing amino acid concentration was elevated in the CLP group (P < 0.05) than in both the control and the shamoperated groups. [³H]-diazepam radioligand binding assays demonstrated that the number of receptors in the septic rats was increased in the forebrain (CLP rats; 2.37 ± 0.04 pmol · mg^{? 1} protein, control rats; 1.45 ± 0.02 pmol · mg^{? 1} protein, sham-operated rats; 1.49 ± 0.03 pmol · mg^{? 1} protein), cerebellum (CLP rats; 1.55 ± 0.05 pmol · mg^{? 1} protein, control rats; 1.05 ± 0.02 pmol · mg^{? 1} protein, sham-operated rats; 1.09 ± 0.02 pmol · mg^{? 1} protein) and brain stem (CLP rats; 1.21 ± 0.04 pmol · mg^{? 1} protein, control rats; 0.61 ± 0.02 pmol · mg^{? 1} protein, sham-operated rats; 0.63 ± 0.02 pmol · mg^{? 1} protein) compared with the control and shamoperated rats (P < 0.05). In conclusion, it was considered that the increased number of benzodiazepine receptors may be one cause of the neuronal alteration observed in septic shock animals.     

Maternal and neonatal effects of bolus administration of ephedrine and phenylephrine during spinal anaesthesia for caesarean delivery: a randomised study

BackgroundMaternal haemodynamic changes and neonatal well-being following bolus administration of ephedrine and phenylephrine were compared in 60 term parturients undergoing elective caesarean delivery under spinal anaesthesia.MethodsIn a randomised double-blind study, women received boluses of either ephedrine 6 mg (group E; n=30) or phenylephrine 100 μg (group P; n=30) whenever maternal systolic pressure was ?80% of baseline.ResultsChanges in systolic pressure were comparable in the two groups. There were no differences in the incidence of bradycardia (group E: 0% vs. group P: 16.7%; P>0.05), nausea (group E: 13% vs. group: P 0; P>0.05) and vomiting (group E: 3.3% vs. group P: 0; P>0.05). Umbilical artery (UA) pH (group E: 7.29 ± 0.04 vs. group P: 7.32 ± 0.04; P=0.01) and venous pH (group E: 7.34 ± 0.04 vs. group P: 7.38 ± 0.05; P=0.002) were significantly greater in group P than in group E. UA base excess was significantly less in group E (-2.83 ± 0.94 mEq/L) than in group P (-1.61 ± 1.04 mEq/L; P<0.001). Apgar scores at 1, 5 and 10min and neurobehavioural scores at 2-4 h, 24 h and 48 h were similar in the two groups (P>0.05).ConclusionsPhenylephrine 100 μg and ephedrine 6 mg had similar efficacy in the treatment of maternal hypotension during spinal anaesthesia for elective caesarean delivery. Neonates in group P had significantly higher umbilical arterial pH and base excess values than those in group E, which is consistent with other studies.     

Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium

Purpose

The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were studied, to evaluate the functional state of the peripheral parasympathetic pathway fol lowing cardiac denervation.

Methods

Edrophonium was studied in patients with normally innervated hearts (controls) and m cardiac trans plants. Edrophonium was also studied in vagotomized. beta-blocked cats. In Group I animals, the vagus nerve was not stimulated. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rate, respectively.

Results

Maximum heart rate reduction in transplants (7.3 ± 0.8 beats·min^?1 with 0.6 ± 0.08 mg·kg^?1) was less than in controls (13.3 ± 1.6 beatsmm with 0.4 + 0.05 mg·kg^?1, P < 0.01). In Group I animals heart rate decreased maximally by 20.9 ± 2.5 beats·min^?1 with 9.0 ± 1.9 mg·kg^?1. In Groups 2 and 3, with doses < 15 mg·kg^?1, reduc tions m heart rate were greater than in Group I and maximual reductions were obtained with lower doses (Group 2: maximum reduction by 20.3 ± 2.8 beats·min^?1 with 1.3 ± 0.1 mg·kg^?1: Group 3: 22.6 ± 4.0 beats·min^?1 with 0.8±0.2 mg·kg^?1, P < 0.001) Doses > 1.5 mg·kg^?1 in Groups 2 and 3 produced increases in heart rate.

Conclusion

Edrophonium produced bradycardia in cardiac transplants suggesting spontaneous release of acetylcholinee from parasympathetic postganglionic neurons m the transplanted heart. The magnitude of the brady cardia was less in transplant than in control patients. Findings from animal studies suggest that the reduction in transplants can be attributed to diminution or absence of tonic cardiac parasympathetic drive. At high doses, edrophonium may interfere with parasympathetic neuron activation.     

Glucose intolerance during prolonged sevoflurane anaesthesia

Purpose

The effects of prolonged sevoflurane anaesthesia on insulin sensitivity were investigated by two successive intravenous glucose tolerance tests (IVGTT) in eight patients who underwent prolonged surgery.

Methods

The first IVGTT was administered (25 g glucose as 20% dextrose in water iv) over two minutes 35 min after initiation of surgery. Arterial blood samples were obtained at 0, 5, 10, 30, 60, and 120 min after glucose administration for blood glucose and plasma insulin determination. A second IVGTT was performed six hours following the initiation of surgery.

Results

The disappearance rate of glucose (k-value) for the first IVGTT was 0.887 ± 0.436 (mean ± SD) % · min^?1, and 0.784 ± 0.289 for the second IVGTT. Both k-values are lower than the normal value. The maximum insulin response to glucose (ΔIRI · ΔBS^?1) of the second IVGTT was lower than the first IVGTT (0.124 ± 0.092 vs 0.071 ± 0.056, P < 0.05). The total insulin output of the first IVGTT was higher than the second IVGTT (1,161 ± 830 vs 568 ± 389 μU · min · ml^?1, P < 0.05).

Conclusion

Glucose intolerance is enhanced by diminished insulin output in response to blood glucose elevation during prolonged anaesthesia and surgery.     

Interaction between succinylcholine and ranitidine in rats

The hypothesis that the histamine H₂ receptor blocker ranitidine potentiates neuromuscular paralysis during anaesthesia was tested in vivo in urethane anaesthetised and mechanically ventilated rats. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 48.5% (±2.5 SEM) tibialis anterior muscle paralysis in 14 rats. Ranitidine 2.5, 5, 10, or 20 mg · kg^?1 iv, was then administered into groups of three or five rats. Ranitidine produced an immediate potentiation of neuromuscular paralysis followed by a transient reversal and then a continued steady-state potentiation. Peak potentiation occurred within 20 (±3.3) sec and was maintained in all the rats to steady-state. Peak reversal was evident 70 (±8.1) sec after ranitidine administration. There was an excellent relationship (r² = 0.98, P < 0.001) between peak potentiation and serum ranitidine concentration with 50% potentiation occurring at 25.8 (±1.1) μg · ml^?1. There was a weak relationship (r² = 0.39, P < 0.05) between peak reversal and serum ranitidine but potentiation at steady-state was not correlated to serum ranitidine concentration (r² = 0.19, P > 0.05). These results show that ranitidine alters the neuromuscular action of succinylcholine in rats in a similar manner to cimetidine.