Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-α (TNF-α), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean ±SD 2717 ±2421 μl^?1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl^?1 (P < 0.01) and remained elevated 7136 ±5194 μl^?1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L^?1 preoperatively) peaked at 1134 ±453 μg · L^?1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · L^?1, after 180 min (P < 0.01). Serum IL-6 level (118 ±59 pg · ml^?1 preoperatively) peaked at 436 ±143 pg · ml^?1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 ±109 pg · ml^?1, after 180 min. Serum IL-8 level (37 ±44 pg · ml^?1 preoperatively) peaked at 169 ±86 pg · ml^?1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 ±78 pg · ml^?1 180 min after declamping of the aorta. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.     

Interleukin-10 and Interleukin-1 receptor antagonists increase during cardiac surgery

Background

It has been reported that inflammatory cytokines such as interleukin-8 and 6 (IL-8, IL-6) increase during cardiac surgery and cause postoperative cardiac dysfunction. Therefore, it is important to investigate changes of suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1 ra) dunng cardiac surgery.

Method

Serum levels of cytokines and IL-1 ra were measured in 10 patients during cardiac surgery with cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia. In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1 ra were measured by enzyme linked immunosorbent assay.

Results

Serum IL-6 and IL-8 concentration (19.1 ±8.8 pg · ml^?1, and 13.4±5.2 pg · ml^?1, preoperatively) increased to 227.5± 191 pg · ml^?1 and 81.0±56 pg · ml^?1 at 60 min after declamping the aorta (P< 0.01, respectively). Serum IL-10 concentration increased at 60 min after dedamping the aorta compared with the preoperative value (from 1.0±0 pg · ml^?1 to 552.0± 158 pg · ml^?1 P< 0.001]). Similarly, serum IL-1 ra concentration increased from the preoperative value of 1331±896 pg · ml^?1 to 43353±12812 pg · ml^?1 at 60 min after dedamping the aorta (P< 0.00l). Positive correlations were obtained between IL-10 and IL-8. and between IL-10 and IL-6 (γ=0.7, γ=0.8, P< 0.001, respectively).

Conclusion

These findings demonstrate that pro-and anti-inflammatory cytokines increase to maintain their balance during cardiac surgery.     

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg · kg^?1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac Junction. Serum concentration of IL-8 in non-MP-treated patients (37 ± 44 pg · ml^?1 preoperatively) increased to 169 ± 86 pg · ml^?1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 ± 8.9 pg · ml^?1 to 52 ± 35 pg · ml^?1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 ± 30 pg · ml^?1 to 436 ± 143 pg · ml^?1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 ± 15 pg · ml^?1 to 135 ± 55 pg · ml^?1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 ± 1.1 L · min^?1· m^?2) was higher than 2.3 ± 0.8 L · min^?1 · m^?2 of non MP-treated patients (P < 0.05). The levels of IL-8 max during surgery correlated negatively with postoperative cardiac index (γ = ?0.67). These results suggest that methylprednisolone suppresses production of IL-8 and 6.     

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.     

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.     

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.     

Epidural administered buprenorphine in the perioperative period

Purpose

To study the effect of epidural buprenorphine on minimum alveolar concentration (MAC) of volatile anaesthetics, duration of analgesia and respiratory function in the perioperative period.

Methods

One hundred and twenty patients, ASA I–II undergoing gynaecological surgery were randomly divided into three studies. The forty patients in each study were randomly divided into four groups depending on the dosage; Group I (control), Group II (80 μg · kg^?1 morphine), Group III (4 μg · kg^?1 buprenorphine), Group IV (8 μg · kg^?1 buprenorphine). The MAC of halothane was measured following epidural administration of the agents in each group. The duration of analgesia was assessed by the first request for pentazocine. Postoperative analgesic effects were assessed by the total dosage of pentazocine required for the 48 hr after surgery. Respiratory rate (RR), minute volume (MV), and PaCO₂ were measured during surgery and the postoperative period. The MAC of halothane was reduced in Group IV (P < 0.01). The duration of analgesia was 10.0 ± 5.1 hr (Mean ± SE) in Group 1, 37.7 ± 4.7 hr in Group II, 27.1 ± 7.1 hr in Group III, and 44.4 ± 4.1 hr in Group IV. Total dosage of pentazocine was lower in Group IV (P < 0.05) than in the other groups. The decrease of RR, MV and the increase of PaCO₂ were observed within 60 min in Group III and IV dose dependently.

Conclusion

Epidural buprenorphine administered in a dose of 4 or 8 μg · kg^?1 provides postoperative analgesia that is no less effective than that of morphine.     

Cardiac implications of amlodipine-dantrolene combinations

Purpose

Cardiac disorders, cardiac arrest and ventricular fibrillation in the most severe cases, have been observed after the administration of dantrolene to patients treated by verapamil for coronary artery disease. This study was designed to examine the interaction of dantrolene with amlodipine, a dihydropyridine.

Methods

In 12 anaesthetized, open-chest pigs, the effects of the interaction have been studied on heart rate, atrioventricular conduction, monophasic action potential duration, intraventricular conduction time, left ventricular dP/dt max and mean blood pressure. The study was performed with normal coronary circulation and ischaemia of a large area of the left ventricule, obtained by complete occlusion of the left anterior descending coronary artery near its origin, under pacing at a constant high rate, 180 beats · min^?1. The drugs were injected iv, amlodipine 0.4 mg · kg^?1 first and dantrolene 3.0 mg · kg^?1 20 min later in six animals and the order was reversed in the other animals.

Results

Sinus rate and atrioventricular conduction were not affected by amlodipine, but were slowed by dantrolene added (145 ±9 to 131 ±7 beats min^?1, P < 0.01 and 150 ± 15 to 180 ± 20 msec, P < 0.01). In contrast, amlodipine or amlodipine plus dantrolene did not change MAP duration or conduction time in the normal heart. Similarly, they did not alter the maximal variations due to ischaemia, but delayed them, while prolonging the time to onset of fibrillation (111 ± 8 to 343 ± 33 sec, P < 0.001 with amlodipine alone, 289 ± 11 to 323 ± 16 sec, P < 0.05 with dantrolene). Left ventricular dP/dt max was lowered from 1670 ± 86 to 1532 ± 50 mmHg · sec^?1 (P < 0.001) and mean blood pressure from 79 ± 4 to 70 ± 3 mmHg (P < 0.01) by amlodipine, but dantrolene did not enhance and even counteracted these effects. Finally, potassium plasma concentration did not increase above 5.1 ± 0.2 mmol · L^?1 under the dual influence of amlodipine and dantrolene.

Conclusion

In usual clinical doses, dantrolene may be safely administered concurrently with amlodipine.     

Topical lidocaine improves conditions for laryngeal mask airway insertion

Purpose

We hypothesized that optimal laryngeal mask airway (LMA?) insertion conditions might be achieved with topical lidocaine and a smaller dose of propofol. In this study, insertion conditions after topical lidocaine 40 mg followed by propofol 2 mg·kg^?1 were compared with propofol 2 mg·kg^?1 or propofol 3 mg·kg^?1 alone.

Methods

Ninety patients were recruited for this randomized prospective double-blind study. One group received four sprays of topical lidocaine (40 mg) over the posterior pharyngeal wall followed by propofol 2 mg·kg^?1 (Group 2PL; n = 30). The other two groups received four sprays of 0.9% normal saline followed by propofol 2 mg·kg^?1 (Group 2P; n = 30) or by propofol 3 mg·kg^?1 (Group 3P; n = 30). The frequency of optimal insertion conditions (successful insertion at the first attempt without adverse responses) and side effects were recorded.

Results

The frequency of optimal insertion conditions was greater in Group 2PL (20/30, 67%) and Group 3P (22/30, 73%) than in Group 2P (11/20, 37%) (P = 0.009). In Group 3P, the mean blood pressure was lower than in the other groups prior to LMA-Classic? insertion (P = 0.003) but was similar after insertion. The incidence of apnea was greater in Group 3P patients (17/30, 57%) than in Group 2P (2/30, 7%) or Group 2PL patients (1/30, 3%) (P < 0.001).

Conclusion

Topical lidocaine 40 mg followed by propofol 2 mg·kg^?1 can provide optimal insertion conditions of the LMA-Classic comparable to those of propofol 3 mg·kg^?1, with fewer hemodynamic changes and a lower incidence of apnea.     

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.     

Fasciculations, myalgia and biochemical changes following succinylcholine with atracurium and lidocaine pretreatment

Purpose

To determine the attenuation in the incidence of myalgia, fasciculations and changes in serum potassium and creatinine kinase concentrations when atracunum and lidocaine were used in combination and separately as pretreatment before succinylcholine.

Method

In a prospective, double blind randomized study, 80 ASA I patients 20–50 yr were assigned to one of four groups. Anaesthesia was induced with thiopentone and fentanyl. Group C received placebo pretreatment before 1.5 mg·kg^?1 succinylcholine: Group A 0.05 mg·kg^?1 atracunum three minutes before; Group L, 1.5 mg·kg^?1 lidocaine 30 sec before; and group AL both atracurium and lidocaine. Serum potassium five minutes after succinylcholine. and creatinine kinase 24 hr after operation were measured and the increases from preinduction values were compared. Fasciculations and postoperative myalgia at 24 and 48 hr were recorded. Patients receivediv mependine orpo paracetamol for postoperative analgesia.

Results

The increase in serum potassium concentration (0.36 ± 0.23 mEq·l^?1) was not attenuated by any regimen (P < 0.05). The incidence of fasciculations (P < 0.05) and the increase in creatinine kinase (P < 0.01) was less in the atracunum (40%; 20.93IU·I^?1) and atracunum-lid ocaine (30%; 22.85IU·I^?1) than in the lidocaine (85%; 45.01IU·I^?1) and control (100%; 56.05 IU·I^?1) groups. Postoperative myalgia on Days 1 and 2 was lowest (P < 0.05) in the atracurium-lidocaine group (5%; 0%) followed by the atracurium (35%; 25%) and lidocaine (30%; 35%) groups and highest in the control (75%; 65%).

Conclusion

Atracurium and lidocaine individually reduce postoperative myalgia, with further decrease occurring when used together.     

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.     

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.     

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.     

Antinociceptive effects of epidural and intravenous ketamine to somatic and visceral stimuli in rats

Purpose

To evaluate the antinociceptive effect of epidural and intravenous ketamine on somatic and visceral stimuli and to address the emergency reaction.

Methods

Rats were randomly allocated into nine groups (n = 6); five groups with chronically implanted epidural catheters received saline or 0.5, 1, 2 and 4 mg · kg^?1 ketamine epidurally, four groups received saline, or 1, 5 and 10 mg · kg^?1 ketamine iv. To assess somatic and visceral antinociceptive effects, tail flick (TF) test and colorectal distension (CD) test were carried out, respectively. Emergence reactions were graded. Maximal possible effects (% MPE) were calculated.

Results

Epidural ketamine increased % MPE in both tests in a dose-dependent fashion for 30 min (vs saline group, P < 0.05). Epidural ketamine 0.5 mg · kg^?1 produced an increase in % MPE in the CD test (P < 0.05) but failed in the TF test. Intravenous ketamine, 10 mg · kg^?1, produced 100 ± 0 (mean ± SE) % MPE in the CD test but 36 ± 15 % MPE in the TF test. Dose response curves indicated greater visceral antinociception than somatic. All rats showed emergence reactions following intravenous ketamine 10 and 5 mg · kg^?1.

Conclusion

Both epidural and intravenous ketamine produce greater antinociceptive effects to visceral than to somatic stimulation, and that epidural ketamine has a low incidence of emergence reactions.     

Somatic paravertebral block decreases opioid requirements in children undergoing appendectomy

Purpose

Somatic paravertebral block (SPVB) appears to provide effective and prolonged nerve block in children; however, study of its use in this population is limited. We compared SPVB with no block in children undergoing appendectomy.

Methods

Thirty-six children aged 3-16 yr undergoing open appendectomy were involved in this prospective randomized controlled study. Anesthesia was induced with propofol and maintained with isoflurane in N₂O/oxygen. All subjects received fentanyl, acetaminophen and ketorolac during anesthesia. Group I (SPVB) subjects received a right SPVB at T₁₁, T₁₂, and L₁ using 0.2% ropivacaine 0.25 mL·kg^?1 with epinephrine 1:200,000 preoperatively. Group II (Control) had only bandaids applied to skin. Both groups were given morphine 0.05 mg·kg^?1 iv every 2 hr if pain scores reached 5/10 on a visual analogue scale. Acetaminophen was administered postoperatively every 6 hr to both groups. Time to first dose of morphine, total dose of morphine in 24 hr, and any adverse effects up to 24 hr after surgery were recorded.

Results

Group I (SPVB) subjects required significantly less morphine than Group II (Control) patients (0.12 ± 0.07 vs 0.34 ± 0.15 mg·kg^?1, respectively; P < 0.001), and time to their first dose was significantly longer (7.1 ± 4.4 vs 2.5 ± 1.6 hr, respectively; P < 0.001). Incidence of vomiting was 11% with Group I and 27% with Group II (P = 0.21). No other adverse effects were observed in either group.

Conclusions

In children undergoing appendectomy, SPVB provides better pain relief than no block and reduces opioid requirements. Side effects were not statistically different between groups.     

Dose-response to anaesthetic induction with sufentanil: haemodynamic and electroencephalographic effects

Purpose

To determine the effect of a five-fold variation in sufentanil dose on the haemodynamic and electroencephalo graphic (EEG) response to anaesthetic induction and tracheal intubation.

Methods

Thirty-four patients undergoing elective coronary artery bypass grafting (CABG) participated in this randomized double-blind study. Patients in Group L (n= 17) received 3 μg · kg^?1 sufentanil and those in Group H (n= 17) 15 μg · kg^?1. Premedication was 60 μg · kg^?1 lorazepam po. Anaesthesia and neuromuscular blockade were induced by infusing sufentanil and 0.15 mg · kg^?1 vecuronium iv over five minutes. Haemodynamic data and the electroencephalographic (EEG) spectral edge were acquired by computer and compared at Control, Induction and Intubation.

Results

Sufentanil dose did not affect the haemodynamic or EEG response at end-induction. No bradyarrhythmias occurred, and the incidence of hypotension was 12% in both groups. However, during induction apparent electromyographic artifacts and a transiently greater increase in heart rate were observed in Group H. The serum sufentanil concentration at Induction was 6.1 ± 1.8 ng · ml^?1 in Group L and 25.4 ± 8.8 ng · ml^?1 in Group H, and did not correlate with haemodynamic changes. No patient recalled any intraoperative event.

Conclusion

Increasing sufentanil dose from 3 to 15 μg · kg^?1 does not influence the ultimate haemodynamic response to induction. Combined with lorazepam premedication, 3 μg · kg^?1 sufentanil produces near-maximal haemodynamic and EEG effects and is adequate for induction and tracheal intubation of patients undergoing CABG. Sufentanil 15 μg · kg^?1 is no more efficacious, and causes transient cardiovascular stimulation.     

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.     

A rapid precurarization technique using rocuronium

Purpose

To evaluate a rapid and time-saving precurarization technique using rocuronium to prevent succinylcholine-induced myalgia.

Method

In a prospective, double blind randomized study, 42 ASA 1–2 patients were assigned to one of three pretreatment groups: 0.01 ml · kg^?1 normal saline, 0.1 mg · kg^?1 atracurium, and 0.1 mg · kg^?1 rocuronium. Anaesthesia commenced with 1.5 μg · kg^?1 fentanyl and 0.5 mg · kg^?1 lidocaine at time zero. Pretreatment was administered 60 sec later, followed by 2.5 mg · kg^?1 propofol. At 90 sec, 1.5 mg · kg^?1 succinylcholine was injected and 30 sec later, the trachea was intubated and the ease of intubation was graded. The patient was observed for the presence and severity of fasciculations. Myalgias were recorded on postoperative days 1, 2 and 7.

Results

The incidence of fasciculations in the rocuronium group (21.4%) was lower (P < 0.001) than atracurium (78.5%) or placebo (92.8%) groups. On postoperative day 1, the incidence of postoperative myalgia in the rocuronium group (14.2%) was less than the placebo group (78.2%;P < 0.002) and atracurium group (85.7%;P < 0.001). The incidence of myalgia in the rocuronium group (7.1%) was lower than in the placebo group (78.5%;P < 0.001) but not different from the atracurium group (42.8%;P = 0.077) on postoperative day 2. On postoperative day 7, there was no difference among the three groups. Fasciculations were related to post-operative myalgia. There was no difference in intubating conditions among the three groups.

Conclusion

Rocuronium pretreatment given just before induction of anaesthesia with propofol reduces fasciculations and succinylcholine-induced myalgia.     

Vomiting after strabismus surgery in children: ondansetronvs propofol

Purpose

To compare the antiemetic efficacy and costs associated with two anaesthetic regimens in children undergoing strabismus surgery. One regimen contained halothane, nitrous oxide and ondansetron, while the other contained propofol and nitrous oxide.

Methods

Three hundred children aged 2–14 yr undergoing strabismus surgery were enrolled into this single-blind, randomized, stratified, blocked study with a balanced design. Anaesthesia was induced by inhalation with halothane/N₂O/O₂ (Group O) or with 2.5–3.5 mg·kg¹ propofol + 0.5 mg·kg^?1 lidocaineiv (Group P). Group O patients were administered 0.15 mg·kg^?1 ondansetron (maximum dose 8 mg)iv and all patients received atropine 20 μg·kg^?1 iv immediately after induction of anaesthesia. Anaesthesia was maintained with N₂O and halothane (Group O) or N₂O and propofol (Group P). Patients were followed for 24 hr after their operation primarily to assess the incidence of postoperative vomiting. For each case, the costs of the anaesthetic drugs administered and their associated intravenous administration tubing were determined. Drug costs were those prevailing at the study site at the time of the investigation. Fixed costs, such as the cost of the anaesthetic equipment were not assessed.

Results

Groups were similar with respect to demographic data. The incidence of vomiting in both groups was 11 % while in-hospital and 23% after discharge. Each episode of in-hospital vomiting prolonged discharge by 17 ± 4 min, P < 0.001. Mean cost per case for anaesthetic drugs was less in Group 0. 18 ± 8vs 21 ± 10 CDN$. mean ± SD. P < 0.01.

Conclusion

The two methods of antiemetic prophylaxis were equally effective. Propofol-based anaesthesia was more expensive.