Cardiovascular changes after naloxone administration in propofol-sedated piglets during opioid overdose.

BACKGROUND: Naloxone is an opioid receptor antagonist. Even when used in modest doses, it has been associated with serious cardiopulmonary side-effects. In this experimental porcine study, we examined the cardiac effects of naloxone during an opioid overdose. METHODS: Cardiac parameters, changes in the left ventricular compliance and the magnitude of catecholamine release were evaluated in eight spontaneously breathing piglets under propofol sedation. Cardiac parameters were recorded every 30 s and transthoracic echocardiography was used for the continuous assessment of cardiac performance. Respiratory arrest was induced by morphine (8 mg/kg). Ten minutes after morphine administration, naloxone (80 microg/kg) was injected intravenously. Every 5 min, arterial blood gases were measured and, every 10 min, a sample for the analysis of plasma catecholamines was drawn. RESULTS: There were no statistically significant changes in left ventricular ejection fraction and no signs of pulmonary hypertension. There was a statistically significant increase in the mean arterial pressure immediately after naloxone administration and in norepinephrine concentration before naloxone administration. After naloxone administration, the plasma catecholamine levels decreased in all but one animal. Two animals developed cardiac arrest (pulseless electrical activity and ventricular fibrillation) shortly after receiving naloxone. Although they were both administered naloxone prematurely due to hypoxic bradycardia, naloxone could have contributed to the development of ventricular fibrillation. CONCLUSION: Naloxone did not cause changes in ejection fraction or mean pulmonary artery pressure in hypoxic and hypercarbic conditions. After naloxone administration, the plasma catecholamine levels returned to baseline in all but one animal, and two animals developed cardiac arrest.

Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled study.

BACKGROUND: Dexmedetomidine (DEX) has been shown to provide good perioperative haemodynamic stability with decreased intraoperative opioid requirements. It may have neural protective effects, and thus may be a suitable anaesthetic adjuvant to neurosurgical anaesthesia. METHODS: Fifty-four patients scheduled for elective surgery of supratentorial brain tumour were randomized to receive in a double-blind manner a continuous DEX infusion (plasma target concentration 0.2 or 0.4 ng ml(-1)) or placebo, beginning 20 min before anaesthesia and continuing until the start of skin closure. The DEX groups received fentanyl 2 microg kg(-1) at the induction of anaesthesia and before the start of operation, the placebo group 4 microg kg(-1), respectively. Anaesthesia was maintained with nitrous oxide in oxygen and isoflurane. RESULTS: The median times from the termination of N2O to extubation were 6 (3-27), 3 (0-20) and 4 (0-13) min in placebo, DEX-0.2 and DEX-0.4 groups, respectively (P<0.05 anova all-over effect). The median percentage of time points when systolic blood pressure was within more or less than 20% of the intraoperative mean was 72, 77 and 85, respectively (P<0.01), DEX-0.4 group differed significantly from the other groups. DEX blunted the tachycardic response to intubation (P<0.01) and the hypertensive response to extubation (P<0.01). DEX-0.4 group differed in the heart rate variability from placebo (93 vs 82%, P<0.01). CONCLUSIONS: DEX increased perioperative haemodynamic stability in patients undergoing brain tumour surgery. Compared with fentanyl, the trachea was extubated [corrected] faster without respiratory depression.

QT interval and QT dispersion during the induction of anaesthesia in patients with subarachnoid haemorrhage: a comparison of thiopental and propofol.

BACKGROUND AND OBJECTIVE: Thiopental prolongs the QT interval more than propofol, and the two induction agents were compared in patients with subarachnoid haemorrhage predisposed to electrocardiographic abnormalities and cardiac dysrhythmias. METHODS: Twenty-nine patients were studied randomly. Anaesthesia was induced with either thiopental or propofol and fentanyl; vecuronium was used as a neuromuscular blocking agent. The electrocardiogram and arterial blood pressure were monitored from before the induction of anaesthesia to 2 min after endotracheal intubation. RESULTS: The median QT interval was at baseline 423 ms in the thiopental group and at 432 ms in the propofol group, and it increased in the thiopental group to 446 ms and decreased in the propofol group to 425 ms (P < 0.01 between groups). After induction and endotracheal intubation, the number of patients with increased QT dispersion was greater in the propofol group (P < 0.05). The incidence of cardiac dysrhythmias was similar in the study groups. CONCLUSIONS: Thiopental and propofol are equally suitable for the induction of anaesthesia in patients with subarachnoid haemorrhage.

Extracranial contribution to cerebral oximetry in brain dead patients: a report of six cases.

The near infrared spectroscopy offers a noninvasive method to monitor regional brain oxygenation. The problem with the technique appears to be possible extacranial contribution to the measurements. As a part of another study, we monitored regional saturation (rSO2) in six brain dead patients either during the test for spontaneous respiration or in those not eligible for organ donation, after discontinuation of mechanical ventilation. Relatively normal rSO2 values were obtained after brain death, and the values decreased concomitantly with the hemoglobin saturation of oxygen (SpO2) after the discontinuation of mechanical ventilation. A corresponding decrease in SpO2 and rSO2 suggests extracranial contribution to the measured rSO2. The diagnosis of brain death cannot be made based on this technology; furthermore the presence of extracranial contribution may limit its potential value even in other applications.

QT dispersion after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) causes a stress response with increased concentrations of plasma catecholamines and serious cardiac arrhythmias. Increased QT dispersion has been shown to predispose to cardiac arrhythmias. In SAH patients, QT dispersion has not been studied previously. QT dispersion was analyzed in 26 patients with SAH and in 16 patients (control group) scheduled for ligation of a nonruptured cerebral aneurysm. In 15 patients with SAH, the plasma concentrations of catecholamines were analyzed, and an 18-hour continuous electrocardiogram (ECG) recording was obtained. In the other 11 patients, electrocardiography was repeated daily for up to 9 days for analysis of QT dispersion. The median (25th and 75th percentiles) QT dispersion in all SAH patients was 78 milliseconds (50 and 109 milliseconds, respectively), and in control patients, it was 25 milliseconds (15 and 33 milliseconds, respectively) (P < .001). There was a positive correlation with QT dispersion and the plasma concentration of DHPG, a metabolite of norepinephrine (P < .05). All patients had episodes of cardiac arrhythmia during the 18-hour recording period. In conclusion, increased QT dispersion is a common finding after SAH and may be a result of high plasma concentrations of catecholamines in these patients.

Patient-controlled analgesia with oxycodone in the treatment of postcraniotomy pain.

BACKGROUND: Moderate to severe pain occurs after craniotomy in 60% of patients. We evaluated the feasibility and safety of patient-controlled analgesia (PCA) with oxycodone in neurosurgical patients, and compared the efficacy of paracetamol with ketoprofen. METHODS: In the study there were 45 patients, who received either paracetamol 1000 mg or ketoprofen 100 mg three times a day. Oxycodone-boluses 0.03 mg/kg were given by PCA-device maximally three times an hour, lock-out time 10 min. The amount of oxycodone used, pain scores and side-effects were recorded. RESULTS: The ketoprofen group required less oxycodone than the paracetamol group (medians 37.1 mg vs 19.6 mg, P < 0.05). The VAS scores were comparable between the groups at the beginning of the study, during the first postoperative evening and the next morning, but the paracetamol group had a higher score at the conclusion of the study (P < 0.05). The patients in both groups were equally satisfied with the pain relief. There were no differences in side-effects between the groups. CONCLUSIONS: PCA with oxycodone is a suitable method for pain control after craniotomy. No progressive hypoventilation, desaturation or excessive sedation were encountered. Ketoprofen appeared to be more effective than paracetamol.

The best view at laryngoscopy using the McCoy laryngoscope with and without cricoid pressure.

The best view obtained by levering the tip of the McCoy laryngoscope blade with or without modified cricoid pressure was studied in 100 patients presenting for general surgery. The airway was assessed pre-operatively (Mallampati score, thyromental distance, mouth opening, protrusion of the jaw and weight) in an attempt to identify the patients who might benefit from the use of the McCoy laryngoscope. The vocal cords were visible at laryngoscopy with the blade in the neutral position in 32 cases. In the 68 remaining patients the vocal cords were partly visible in 48. The epiglottis only was seen in 18 patients and in two not even the epiglottis could be visualised. Elevation of the blade or modified cricoid pressure improved the view in 38/68 cases and 57/68 cases, respectively (p < 0.001, Wilcoxon signed rank). Using our method of pre-operative assessment we were unable to identify those patients who might benefit from either manipulation.

The relevance of clinical and radiological measurements in predicting difficulties in fibreoptic orotracheal intubation in adults.

Resistance to the passage of the tracheal tube has been reported to occur in up to 36% of patients subjected to orotracheal fibreoptic intubation. In this prospective study we assessed five radiological measurements of the upper airway in an attempt to find anatomical causes of obstruction to passage of the tube. Forty-nine patients undergoing fibreoptic orotracheal intubation under general anaesthesia were studied. Pre-operatively, the Mallampati grade and the thyromental distance were assessed. The plain films, CT scans or MR images of the cervical spine were used for measurement of the position of the vocal cords, the length of the epiglottis and the size of the tongue. The resistance to the passage of the tube was graded as none, mild, moderate or severe. The length of the epiglottis and the size of the tongue, but not the position of the vocal cords, had positive correlations with the severity of impingement. The pre-operative bedside tests did not correlate with difficulties in fibreoptic intubation.

The effect of patient positioning on dynamic lung compliance.

BACKGROUND: Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS: The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS: The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION: We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

Knee-chest vs horizontal side position during induction of spinal anaesthesia in patients undergoing lumbar disc surgery.

In the prone knee-chest position the spread of plain 0.5% bupivacaine in the cerebrospinal fluid and associated haemodynamic changes may be different compared with the horizontal position. A randomized comparison was performed in 40 ASA I-II patients, aged 24-61 yr, undergoing lumbar disc surgery. Subarachnoid injection (27-gauge needle) at the L2-3 interspace with 3 ml of 0.5% bupivacaine was performed with the patient in the operative knee-chest position (prone knee-chest group, n = 20) or in the horizontal side position (supine side horizontal group, n = 20). Patients in the supine side horizontal group were turned into the horizontal supine position for 20 min, and subsequently they were placed in the operative knee-chest position. In three patients in the prone knee-chest group, the spinal needle was replaced by a larger needle (25-gauge). The final cephalad extension of sensory analgesia on skin tested by pinprick was T5 (median) in the prone knee-chest group and T6 in the supine side horizontal group. Recovery was also similar, on average 210 min from injection in both groups. The mean decrease in systolic arterial pressure was somewhat greater in the prone knee-chest group (30 mm Hg) than in the supine side horizontal group (13 mm Hg). The need for ephedrine occurred earlier in the supine side horizontal group (three patients, all within 10 min from local anaesthetic injection) than in the prone knee-chest group (six patients, all after 15 min). Four of the latter patients also required administration of an anticholinergic for bradycardia compared with two patients in the supine side horizontal group. Light sedation was given to five patients in the prone knee-chest group and to four in the supine side horizontal group because of numbness and aching in the shoulders. We conclude that spinal block was similar in the two groups but there was a tendency to more frequent episodes of haemodynamic deterioration in the knee-chest position.

Comparison of the effects of controlled ventilation with 100% oxygen, 50% oxygen in nitrogen, and 50% oxygen in nitrous oxide on responses to venous air embolism in pigs.

In this randomized, experimental study in 18 pigs, we have investigated the effects of inspiratory air in oxygen, 100% oxygen and 50% nitrous oxide in oxygen on the detection and consequences of venous air embolism. Each animal was tested with injections of 1.0 ml kg-1 and 2.0 ml kg-1 of air. All animals, except one in the nitrous oxide group, survived the air emboli. Systolic and diastolic arterial pressures decreased significantly in all groups after both injections of air. Pulmonary diastolic pressures increased most in the nitrous oxide group. End-tidal concentration of carbon dioxide decreased significantly in all groups after air injections. The difference in concentration of oxygen in the inspiratory and expiratory gas (O2 (I-E)) was lowest in the air group after both injections of air. On the basis of our studies we suggest that nitrous oxide should not be used during surgery associated with an increased risk of venous air embolism.

Monitoring lung compliance and end-tidal oxygen content for the detection of venous air embolism.

Venous air embolism (VAE) is a recognized complication of surgery performed with the patient in the sitting position, but it occurs also during other operations. We report two cases of VAE, associated with a notable decrease in dynamic lung compliance, detected by side-stream spirometry. Based on these cases, an experiment with 10 pigs was designed to evaluate the usefulness of side-stream spirometry in the diagnosis of VAE. Three doses of air (0.5, 1.0 and 2.0 ml kg-1) were injected via the proximal part of a 5- French gauge pulmonary artery catheter. Only the largest dose was followed by haemodynamic deterioration. Significant increases in end-tidal oxygen content and decreases in dynamic lung compliance were detected with all doses of air together with conventional signs of VAE, that is increases in pulmonary artery pressures and arterial carbon dioxide tensions, and decreases in end-tidal concentration of carbon dioxide. We conclude that continuous monitoring of end-tidal oxygen concentration and side-stream spirometry offers valuable supplements to other monitoring techniques in the detection of VAE.

Anaphylactoid skin reactions after intravenous regional anaesthesia using 0.5% prilocaine with or without preservative--a double-blind study.

Methylparaben, the preservative of various local anaesthetic solutions, is a potential allergen. In a double-blind study, 0.5% prilocaine with (Citanest, n = 100) or without (n = 100) methylparaben were compared for the occurrence of skin reactions after intravenous regional anaesthesia of the arm in surgical patients. Skin reactions were registered after the deflation of the tourniquet cuff, and intradermal tests were performed with 0.5% prilocaine, 0.1% methylparaben and saline in all patients. Seventeen patients in the Citanest group and four patients in the methylparaben-free prilocaine group developed erythematous skin reactions in the exposed arm after deflation of the tourniquet cuff (P < 0.05, between the groups). The skin symptoms disappeared within an hour and were always restricted to the region which had been anaesthetised. None of the affected patients had positive intradermal tests. The observed skin reactions are probably non-IgE-mediated anaphylactoid reactions in which the presence of methylparaben in the local anaesthetic solution plays a major role.

Comparison of 2-chloroprocaine and prilocaine for intravenous regional anaesthesia of the arm: a clinical study.

In a double-blind, randomised study of patients scheduled for minor hand surgery 0.5% 2-chloroprocaine (n = 30) and 0.5% prilocaine (n = 30) in a volume of 40 ml were compared for intravenous regional anaesthesia. The onset of sensory and motor block and recovery of sensory block were determined, and the occurrence of side-effects was noted. Twenty-four patients in the 2-chloroprocaine group and 17 in the prilocaine group developed complete sensory block by 15 min after injection (p < 0.05). Complete recovery of sensation was faster after prilocaine (7.1 min) than 2-chloroprocaine (9.8 min) (p < 0.01). Venous irritation and/or urticaria after tourniquet release was observed on 10 occasions in those receiving 2-chloroprocaine and twice in those receiving prilocaine. An increase in heart rate of > 20% above control values occurred in three patients, all of whom had been given 2-chloroprocaine. Clinically, local anaesthetic properties of 0.5% 2-chloroprocaine and prilocaine were similar, but there were more side-effects with the former drug.

The effect of amrinone on recovery from severe bupivacaine intoxication in pigs.

Cardiovascular collapse following intravascular bupivacaine may be resistant to treatment. The effect of amrinone on recovery from bupivacaine-induced severe cardiovascular depression was evaluated in 20 pigs (13-26 kg) in a placebo-controlled randomized double-blind study. Under 0.7% isoflurane anesthesia at FIO2 0.21, 0.5% bupivacaine 2 mg.kg-1.min-1 was infused until mean arterial pressure was 40% of the baseline. Cardiac output and heart rate decreased 75% and 50% from the baseline, respectively. The total dose of bupivacaine was 17 +/- 6 (SD) mg.kg-1 in the control and 19 +/- 5 mg.kg-1 in the amrinone group, resulting in mean plasma concentrations of 42 +/- 6 and 53 +/- 19 micrograms.ml-1, respectively. A bolus of amrinone 4 mg.kg-1 (n = 10) was given immediately after cardiovascular depression, followed by an infusion of 0.6 mg.kg-1.min-1. The control animals received corresponding volumes of physiologic saline (n = 10). After cardiovascular depression, the lungs were ventilated with FIO2 1.0 without anaesthetics or sympathomimetic support. Electric activity of the heart ceased in all control animals in 3.9 +/- 2 min after cardiovascular depression despite atropine and external cardiac compression. All animals in the control group and 5 of 10 animals in the amrinone group were given atropine (P less than 0.01). The animals receiving amrinone survived without cardiac compression (P less than 0.0001). During bupivacaine infusion, all animals developed burst suppression in the electroencephalogram. At the time of cardiovascular depression, in 8 of 10 control and in 6 of 10 amrinone animals, the electroencephalogram was isoelectric.(ABSTRACT TRUNCATED AT 250 WORDS)

A rodent model for studying four well defined toxic endpoints during bupivacaine infusion.

An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% O2 and 70% N2O. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg +/- SD) precipitating AAR, SZ, ISO EEG and ASYS were 4.22 +/- 1.87, 7.08 +/- 1.55, 11.05 +/- 5.15 and 20.4 +/- 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p greater than 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other (p greater than 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs.

Cardiovascular and central nervous system effects of co-administered lidocaine and bupivacaine in piglets.

The toxic profile of bupivacaine (1 mg/kg/minute) when administered intravenously alone or with lidocaine (1 mg/kg loading dose, then 1 mg/kg/minute) was examined in 12 2-day-old pigs anesthetized with 70% N2O/30% O2 and paralyzed with 0.15 mg/kg pancuronium. Bupivacaine doses producing arrhythmias, seizures, isoelectric EEG and asystole were about 24% lower in the lidocaine plus bupivacaine group (n = 6) than in the bupivacaine group (n = 6). However, the incidence of cardiac arrhythmias in the combination local anesthetic group (3/6) was half that in the bupivacaine group (6/6). Administration of lidocaine with bupivacaine under conditions of this study apparently reduces the risk of cardiac arrhythmias and acts along with bupivacaine to produce seizures, cerebral depression (isoelectric EEG) and asystole.

Bupivacaine toxicity in young pigs is age-dependent and is affected by volatile anesthetics.

The influence of age and volatile anesthetic agents on plasma concentrations and toxic effects of bupivacaine were studied in 2-day-old, 2-week-old, and 2-month-old pigs. Bupivacaine was infused at a constant rate while the pigs' ECGs and EEGs were recorded. Six pigs in each age group were lightly anesthetized with 70% N2O/30% O2 during the bupivacaine infusion, and twelve 2-day-old pigs were anesthetized with 70% N2O/30% O2 plus either 0.5 X MAC halothane or isoflurane. Two-day-old pigs were more resistant than older pigs to the toxic effects of bupivacaine despite higher plasma concentrations at all sample times. All pigs given N2O alone or N2O plus halothane had ventricular dysrhythmias, but only one pig in the N2O plus isoflurane group had a ventricular dysrhythmia. Threshold doses of bupivacaine for dysrhythmias in the N2O alone and N2O plus halothane groups did not differ. Seizures occurred in all pigs in the N2O alone group, in none of the N2O plus halothane group, and in two of the N2O plus isoflurane group. The doses required to depress cardiac index and cause asystole were less in the groups receiving halothane and isoflurane. It was concluded that N2O plus halothane and N2O plus isoflurane increase the lethality of bupivacaine while preventing early warning signs of toxicity.

Treatment of bupivacaine-induced cardiac arrhythmias in hypoxic and hypercarbic pigs with amiodarone or bretylium.

The treatment of bupivacaine-induced cardiovascular toxicity with amiodarone or bretylium was studied using anesthetized pigs (n = 30). The pigs were given ketamine, glycopyrrolate, enflurane, and pancuronium and made hypoxic (FiO2, 12%; N2O, 88%) and hypercarbic (end-tidal CO2, 7.3-8.0%) before the administration of bupivacaine (4 mg/kg i.v.). The animals were then treated, in a randomized and double-blind fashion, with either amiodarone (n = 10) 10 mg/kg in 5% dextrose solution i.v. followed by a constant infusion of 15 mg/hour, bretylium (n = 10) 20 mg/kg in 5% dextrose solution i.v. followed by a constant infusion of 90 mg/hour, or 5% dextrose solution (n = 10). The animals were resuscitated, if required. After 30 minutes of recovery, the animals that survived were made hypoxic and hypercarbic again and given a second injection of bupivacaine (2 mg/kg IV). Bupivacaine caused marked changes in the ECG; polymorphic ventricular tachycardia (20 cases) or severe bradycardia that resulted in asystole (10 cases). Nine animals out of ten treated with amiodarone survived (stable sinus rhythm, arterial blood pressure at near control level, normocarbia), whereas six animals in the bretylium group and four in the control group died. The difference in survival between the groups was not, however, statistically significant.

Interaction of lidocaine and hypothermia in Bier blocks in volunteers.

The present investigation was designed to study the interaction of temperature, lidocaine, and ischemia during intravenous regional anesthesia (IVRA) of the arm. Five volunteers were studied during exposure of one of their arms to four different experimental conditions: hypothermia and ischemia; hypothermia, ischemia, and lidocaine; normothermia and ischemia; normothermia, ischemia, and lidocaine. Each subject was tested on four different occasions with only one test condition imposed per occasion and with 3 or more days between experiments. Somatosensory evoked responses (SERs) and muscle responses to ulnar nerve stimulation were measured, and sensory testing was done to determine whether the neural effects of the particular treatments differed. Anesthesia developed sooner and was more extensive when local anesthetic was injected. A 5-10 degrees C decrease in tissue temperature did not accentuate the anesthetic effects of lidocaine as determined by time to loss of pinprick and touch sensation. With ischemia alone, anesthesia of the finger tips with preservation of sensation on the arm was observed in all subjects 20 min after tourniquet inflation. Anesthesia at all cutaneous test sites was achieved in 7 of 10 lidocaine experiments; no systematic order of sensory loss, such as progression from distal to proximal sites, was observed. Decrease in limb temperature slowed the development of lidocaine effects on evoked responses and recovery from the effect. Under conditions of ischemia, deterioration of sensation generally began earlier under cold rather than warm conditions. Primary differences between changes in the SERs and muscle responses under condition of ischemia versus ischemia and lidocaine were the rate and magnitude of change of potential latency and amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)