A randomized comparison of low-dose ketamine and lignocaine infiltration with ketamine-diazepam anaesthesia for post partum tubal ligation in Vanuatu

Ketamine remains one of the most commonly used anaesthetic agents around the world. Despite it being the anaesthetic agent of choice in many developing nations, there is a paucity of literature describing ketamine in the developing world. In what we believe is the first randomized controlled trial to be performed in Vanuatu (formerly the New Hebrides) we compared the use of ketamine 0.9 mg/kg and diazepam 0.07 mg/kg with ketamine 0.3 mg/kg and 2% lignocaine infiltration in 50 Melanesian women undergoing post partum tubal ligation. All women received 0.5 mg/kg intramuscular pethidine. Visual analog pain scores and verbal numeric satisfaction scores were similar between the groups. However the time to obeyed command was significantly faster in the 0.3 mg/kg ketamine group (7.0+/-4.9 vs 13.0+/-9.2 min). The incidence of dreaming was similar and the content rated as pleasant by both groups. In institutions where post-anaesthesia care resources are limited, 0.3 mg/kg ketamine with local anaesthesia provides for earlier self-care of patients after tubal ligation, without compromise of analgesia, emergence or satisfaction. The implications of these findings extend to other procedures that require short general anaesthesia, which can be adequately performed with low-dose ketamine and local anaesthesia. The latter technique allows more rapid awakening.     

Effect of Vecuronium and Pancuronium on Cardiac Performance and Transmural Myocardial Perfusion During Ketamine Anaesthesia

The haemodynamic effects of vecuronium and pancuronium were studied in 20 healthy patients during diazepam/ketamine anaesthesia. Anaesthesia was induced with glycopyrrolate 3 micrograms/kg, diazepam 0.3 mg/kg and ketamine 1.0 mg/kg as a bolus and 1.0 mg/kg over 10 min. After induction, anaesthesia was maintained with ketamine infusion 1.0 mg/kg/h. The lungs were ventilated with 50% nitrous oxide in oxygen. Equipotent doses of vecuronium (74 micrograms/kg) or pancuronium (99 micrograms/kg) were administered for intubation. The thoracic impedance, ECG and phonocardiogram were recorded during the induction of anaesthesia. The results suggest that vecuronium has no cardiovascular effects during ketamine anaesthesia, whereas pancuronium due to its chronotropic effect, causes a deterioration in left ventricular performance.     

Ketamine as Induction Agent for Caesarean Section

A series of 100 patients undergoing caesarean section was studied using ketamine 1.2 mg/kg as induction agent. Fifteen minutes prior to induction, atropine 0.25-0.5 mg and diazepam 1 mg was given intravenously as premedication. Anaesthesia was maintained with N₂O:O₂, FIO₂ 0.4. Once the umbilical cord was clamped, 0.2 mg fentanyl and 9 mg diazepam was given intravenously. Except for nitrous oxide, no more anaesthetic intravenous or inhalational agent was needed. Despite the fact that patients with known intrauterine asphyxia before the induction were included in the material, we found excellent Apgar scores (mean 9.1 at 1 min and 9.9 at 5 min). None of the patients reported awareness during the operation. Eight patients experienced pleasant dreams and three unpleasant. There were no hallucinations in the recovery area. The mental condition of the mothers after the operation was acceptable. It is suggested that ketamine can be used not only on special indications but also as a routine method for induction of anaesthesia for caesarean section.     

Effect of different anaesthetics,routes of catheterisation,age, and filling rate on the urodynamics of the guinea-pig

This study compared the effects of two anaesthetic regimens, ketamine 66 mg/kg with xylazine 2.5 mg/kg and urethane 1.25 g/kg, on the urodynamic parameters of the guineapig. In addition, the effects of advancing age, different filling rates (0.25 and 0.5 ml/min) and different routes of cannulation of the bladder (urethral and suprapubic) upon urodynamic parameters were studied. There was a larger cystometric capacity under urethane than with ketamine and xylazine anaesthesia in both young and old animals. Older animals had a larger cystometric capacity under ketamine and xylazine anaesthesia and a higher pressure threshold (P_threshold) for micturition under urethane. The higher filling rate, 0.5 ml/min, caused a higher P_threshold under ketamine and xylazine anaesthesia. There was a significantly higher voiding pressure with the urethral catheter in place, than with a suprapubic catheter alone. There was also a lower P_threshold when recording with a suprapubic catheter than with a urethral catheter under ketamine and xylazine anaesthesia (5.4 vs. 1.8 cm H₂O). Interpretation of the results from anaesthetised small animal models should take into account the age of the animal, the anaesthetic used and the route by which the various parameters are measured. © 1992 Wiley-Liss, Inc.     

Plasma Free Norepinephrine and Epinephrine Concentrations Following Diazepam-Ketamine Induction in Patients Undergoing Cardiac Surgery

Ketamine causes cardiovascular stimulation, presumably, by increasing central sympathetic activity. This study was undertaken to find out if diazepam in appropriate doses could abolish or moderate the central sympathetic and cardiovascular stimulation following ketamine in patients undergoing cardiac surgery. Twelve patients, scheduled for valvular replacement (8) and direct aortocoronary bypass graft operations (4) were studied. After premedication with diazepam 0.15 mg/kg orally and morphine sulphate 0.15 mg/kg i.m., they were induced with diazepam 0.3 mg/kg i.v., followed 10 min later by ketamine 2 mg/kg i.v. Direct arterial pressure by a strain gauge from the radial artery and heart rate by EKG were continuously recorded. Plasma free norepinephrine, measured by Vendsalu's method, in the arterial blood was 0.39 +/- 0.03 ng/ml prior to induction, 0.39 +/- 0.03 ng/ml 10 min after diazepam and 0.42 +/- 0.05 ng/ml (P greater than 0.05) 5 min after ketamine administration. Plasma free epinephrine concentrations were 0.10 +/- 0.04 ng/ml prior to induction, 0.06 +/- 0.03 ng/ml (P less than 0.05) 10 min after diazepam and 0.01 +/- 0.003 ng/ml (P less than 0.05) 5 min after ketamine. Heart rate and systolic pressure did not change significantly throughout the study period. Diastolic pressures were elevated significantly (P less than 0.05) 5 min after ketamine administration, amounting to a 12% increase over baseline. Diazepam-ketamine induction in cardiac surgical patients did not result in clinically significant central sympathetic or cardiovascular stimulation.     

Continuous interscalene brachial plexus block during and after shoulder surgery

Continuous interscalene brachial plexus block with a single dose of 0.75% bupivacaine (150-210 mg) with adrenaline, continued with an infusion of plain 0.25% bupivacaine 0.25 mg/kg/h, was performed on 20 patients to provide analgesia during shoulder surgery and in the postoperative period. The control group included 20 patients who were given general anaesthesia for surgery after starting a continuous interscalene brachial plexus block; test dose of 0.75% bupivacaine (22.5 mg) with adrenaline, continued with an infusion of 0.25% bupivacaine 0.25 mg/kg/h. Surgery was performed successfully under regional anaesthesia in 16/20 patients; 4/16 were given one dose of fentanyl during the surgery, and diazepam or midazolam as supplementary sedation were given in 13/16 cases. For postoperative analgesia 35/40 patients had a fully functioning catheter for 20-26 hours and the need for oxycodone i.m. during that time was 1.5 +/- 0.4 doses after regional anaesthesia (n = 14) and 1.8 +/- 0.4 doses after general anaesthesia (n = 18). There was a statistically significant difference in the mean plasma bupivacaine concentrations between the groups, concentrations in the regional anaesthesia group being higher at 5, 30, 60 min and 3 h (maximum 2.3 micrograms/ml at 60 min), but there was no difference between the values at 24 h. One infusion of local anaesthetic was discontinued because of probable treatment-related side-effects (breathing difficulties, nausea). Mild local anaesthetic toxicity (dizziness, tinnitus) was noticed in four patients.     

Oral midazolam is an effective premedication for children having day-stay anaesthesia.

The effect of oral premedication was studied in a double-blind, randomised trial of 200 children undergoing day-stay anaesthesia. Midazolam 0.25 mg/kg, midazolam 0.5 mg/kg, diazepam 0.5 mg/kg or a placebo was given orally one hour prior to anaesthesia. Patient state was assessed at nine stages, from administration of the premedication up to and including induction of anaesthesia, using a four-point behavioural scale. Patient state was also assessed postoperatively in the recovery area and the day-stay ward. There was no difference between the four groups until induction of anaesthesia. At this stage 82% of children were either asleep or awake and calm. Patients who received midazolam 0.5 mg/kg were more likely to be asleep or awake and calm at induction rather than other groups (P = 0.05). Children receiving midazolam 0.5 mg/kg or diazepam 0.5 mg/kg slept longest in the post anaesthetic recovery room (P less than 0.005), and spent most time there (P less than .005). There was no difference between groups in the length of time spent in the day-stay ward or in the number of overnight admissions. The study shows that a high proportion of unsedated children are calm at induction of anaesthesia and that oral midazolam is an effective premedication in children for day-stay anaesthesia.     

Ketamine: a new look to an old drug

Ketamine is an NMDA receptors antagonist, with a potent anaesthetic effect. NMDA receptors are involved in nociceptive modulation, in the wind-up phenomenon, in peripheral receptive fields expansion, in primary and secondary hyperalgesia, in neuronal plasticity. Ketamine effects are well-known: it produces a state of "dissociative anaesthesia", amnesia, and, at the same time, it mantains the respiratory drive effective and supports the sistemic arterial blood pressure. Anaesthesiologists are also familiar with its side-effects, like the increase of salivar and bronchial secretions, the possible increase of intracranial and pulmonary pressures and the dysphoric effect that may produce vivid and sometimes unpleasant dreams. Reviewing scientific data and studies about the use of ketamine in children, many considerations come out: at first they considered the effects of the racemic ketamine, then they evaluated the S-enantiomer. Many surveys studied the effects (analgesia, sedation, side-effects) of different doses or different routes of administration. Other studies were designed to compare ketamine to clonidine or opioids as adjuvants in paediatric regional anaesthesia with local anesthetic drugs, in order to prolong analgesia. In our Children's Hospital, we use ketamine in the operating room, in intensive care unit and for any procedure in hospital wards. The suggested doses are: Epidural or caudal route (as an ajuvant for local anaesthetic agents, in the treatment of postoperative pain): 0.5 mg/kg. Sedative/analgesic effect (for algesic procedures): 1-2 mg/kg i.v. Continuous infusion (intensive care unit): 0.5 mg/kg/h, with a range from 20-30 microg/kg/min to 80 microg/kg/min, depending on the age of the patient.     

Rectal premedication in children

Two hundred and eight healthy children who were to undergo minor elective surgery during halothane, nitrous oxide, oxygen anaesthesia were studied in a double blind investigation to evaluate the sedative and anticholinergic effects of two rectal premedications. Group I received diazepam 0.75 mg/kg rectally; Group II received a mixture of diazepam 0.5 mg/kg, morphine 0.15 mg/kg and hyoscine 0.01 mg/kg rectally. No significant difference was found between the two groups in sedative or anticholinergic effects during induction of anaesthesia or in the postoperative period. No adverse effects were seen.     

Use of ketamine in acute severe asthma

Two patients with acute severe asthma, who failed to respond to conventional therapy, were given intravenous ketamine in sub-anaesthetic doses with good results. A bolus dose of 0.75 mg/kg was followed by the same dose over 10 min with relief of bronchospasm in both cases. An infusion of ketamine at a rate of 0.15 mg/kg/h was used in each case to prevent recurrence of bronchospasm. Intravenous ketamine can be used to relieve acute intractable bronchospasm provided expert anaesthetic help is at hand. A review of the literature concerning its use in such situations is also presented.     

Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam

Ro 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED 100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 mg/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.     

Rectal administration of midazolam as an adjuvant in the premedication of infants

In a randomized, double-blind study of premedication in 69 infants aged between 13 and 48 months the effects of 0.82 mg/kg midazolam or diazepam rectally plus 2.0 mg/kg ketamine i.m., or the administration of 2.4 mg/kg ketamine i.m. alone was studied. A satisfying result of 94.1% following the premedication with midazolam/ketamine, of 82.9% with diazepam/ketamine and of 81.3% with ketamine alone was observed. Premedication with midazolam/ketamine was the best one in the review of vigilance, agitation, and behaviour of defence against the mask at the beginning of anaesthesia. The amnestic action of midazolam extinguished the infants' memory of the i.m.-injection. The dose of midazolam/ketamine is suitable as an effective and positive method for premedication of infants within 20 min.     

A comparison between local anaesthetic dorsal nerve block and caudal bupivacaine with ketamine for paediatric circumcision

BACKGROUND: Ketamine has been shown to prolong analgesia produced by caudal local anaesthetic block and is now in common use. This study compares caudal block using bupivacaine/ketamine with dorsal nerve block of the penis. METHODS: Sixty boys undergoing elective circumcision were given either 0.5 ml x kg-1 of bupivacaine 0.15% with ketamine 0.5 mg x kg-1 (n = 30) or dorsal nerve block of the penis with bupivacaine 0.5% (n = 30) as a supplement to general anaesthesia. Postoperative pain was assessed by parents using a modified objective pain score, and the time taken to first requirement of analgesia was recorded. Motor weakness, time to first micturition, postoperative nausea and vomiting (PONV), eating habits, sleep disturbance and behaviour were also assessed. RESULTS: There was no difference between the groups in time to first requirement for analgesia or number of doses of paracetamol given in the first 24 h. Almost half the boys in the caudal group had motor weakness, and there was a significant increase in time to first micturition in that group. There was no difference between the groups in PONV, eating, sleeping or behavioural disturbance. CONCLUSIONS: Caudal anaesthesia with bupivacaine/ketamine does not confer any advantage over a dorsal nerve block with the doses used in this study. Because of the higher incidence of side-effects and technique failure in the caudal group, dorsal nerve block is perhaps the preferred technique.     

EFFECT OF NALOXONE ON THE LOSS OF CONSCIOUSNESS INDUCED BY I.V. ANAESTHETIC AGENTS IN MAN

The effect of a specific opioid antagonist, naloxone, was studiedin two comparable groups of patients who received i.v. the doseof an anaesthetic agent required to produce loss of consciousnessin 50% of subjects. The first group received naloxone 0.006mg kg^–1 5 min before induction of anaesthesia; the secondgroup received a similar volume of saline solution. Thiopentone,Althesin, diazepam, ketamine and propanidid were studied. Thedifferences in percentage of unconscious patients between thenaloxone-treated group and the control group were statisticallysignificant for diazepam, ketamine and propanidid. Naloxonedid not modify the induction of anaesthesia with thiopentoneor Althesin     

Ketamine in war/tropical surgery (a final tribute to the racemic mixture)

A technique of continuous intravenous anaesthesia with ketamine was used successfully during the Somalia civil war in 1994 and in north Uganda in 1999 for 64 operations in 62 patients, aged from 6 weeks to 70 years, undergoing limb and abdominal surgery including caesarian sections and interventions in neonates. Operations lasting up to 2h could be performed in the absence of sophisticated equipment such as pulse oximeters or ventilators in patients on spontaneous ventilation breathing air/oxygen only. After premedication with diazepam, glycopyrrolate and local anaesthesia, and induction with standard doses of ketamine, a maintenance dose of 10-20 microg/kg/min of ketamine proved safe and effective. Emphasis was placed on bedside clinical monitoring, relying heavily on the heart rate. Diazepam, unless contraindicated or risky, remains the only necessary complementary drug to ketamine as it buffers its cardiovascular response and decreases the duration and intensity of operative and postoperative hallucinations. Local anaesthetic blocks were useful in decreasing the requirement for postoperative analgesia. An antisialogue was usually unnecessary in operations lasting up to 2 h, glycopyrrolate being the best choice for its lowest psychotropic and chronotropic effects, especially in a hot climate. Experience in war/tropical settings suggests this technique could be useful in civilian contexts such as outdoor life-saving emergency surgery or in mass casualties where, e.g. amputation and rapid extrication were required.     

Evaluation of 2 modalities of use of propofol in cerebral angiography

Fifty eight adult patients suffering from different intracranial lesions and scheduled for cerebral angiography were given propofol. In the first group (38 patients) brief periods of anaesthesia were induced and reinduced by means of 1.5 mg/kg of propofol iv and sometimes extended with boluses of 25-50 mg of this anesthetic. The patients were premedicated with 0.5 mg atropine im 30-40 min before the induction. Fentanyl, droperidol and diazepam in various combinations and doses were injected, im together with the atropine and iv 1-2 min before the induction, to obtain long-lasting sedations. In the second group (20 patients) the induction of the anaesthesia started 20-35 min after 0.5 mg of atropine im and 1 min after 0.1 mg of fentanyl iv. The induction was based on a bolus of 2.5 mg/kg of propofol and it was followed by suxamethonium, tracheal intubation and mechanical ventilation with N2O 70% in O2. An adequate depth of anaesthesia was maintained with supplemental doses of 50 mg of propofol, frequently associated with 25 mg of suxamethonium. Both methods proved to be reliable and safe. Nevertheless, the second method provided a better stability as far as a number of physiologic variables is concerned.     

Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy

Few studies exist of using remifentanil and intravenous ketamine for anaesthetic induction in paediatric day case anaesthesia. Therefore, we studied 75 unpremedicated ASA I-II children (age 1-7 years) who were randomly assigned in a double-blind fashion to receive either remifentanil (1 microgram/kg), ketamine (0.7 mg/kg) or placebo before the anaesthetic induction. Anaesthesia was induced with propofol and maintained with O2-N2O-sevoflurane. Induction characteristics, recovery times and the need for postoperative analgesia were evaluated. The required induction dose of propofol was lower in the groups receiving remifentanil and ketamine compared with the group receiving placebo. After tracheal intubation heart rate and blood pressure were better attenuated with remifentanil than with ketamine or placebo. In the recovery room children in the placebo group required more doses of oxycodone than the other two groups but this did not reach statistical significance. There were no differences between the groups in achieving predetermined recovery end-points, attaining full points on the Steward score or in the well being at home. In conclusion, remifentanil provides haemodynamically more stable induction of anaesthesia compared with ketamine or placebo. Ketamine with its' longer duration of action does not prolong recovery but does not have a clear opioid-sparing effect either in the immediate postoperative period.     

Atividade simpática de cetamina S‐(+) em doses baixas no espaço epidural

Background and objectives

S‐(+)‐ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S‐(+)‐ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S‐(+)‐ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block.

Methods

The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine) was given to one group (control group) while local anaesthesia and S‐(+)‐ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non‐competitive enzyme immunochemistry method (Cat Combi ELISA) was used to determine the concentrations of catecholamines (adrenaline and noradrenaline). Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann–Whitney U‐test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects.

Results

40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S‐(+)‐ketamine. Value p < 0.05 has been taken as a limit of statistical significance.

Conclusions

Low dose of S‐(+)‐ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S‐(+)‐ketamine administered epidurally did not deepen sympathetic block. Adding 25 mg of S‐(+)‐ketamine to 0.5% bupivacaine does not deprive sympathetic tonus below the level of epidural block at the moment of most expressed sympathetic block and has no effect on sympathetic tonus above the block level.     

Intravenous ketamine for prevention of severe hypotension during spinal anaesthesia

Spinal block causes paralysis of preganglionic sympathetic fibres, while ketamine induces activation of the sympathetic nervous system. Hypotension is a frequent complication during spinal anaesthesia and is associated with an increased risk of postoperative mortality. The aim of our study was to compare circulatory changes in patients who received either fentanyl or ketamine during spinal anaesthesia. Thirty patients (ASA I-III) scheduled to undergo spinal anaesthesia for osteosynthesis of hip fractures were allocated to receive either ketamine or fentanyl intravenously during the procedure. Immediately before anaesthesia, 7 ml/kg BW of an isotonic NaCl solution was administered i.v. Patients received either fentanyl 1.5 mg/kg BW i.v. before anaesthesia, or ketamine 0.7 mg/kg BW i.v. before anaesthesia, and 0.35 mg/kg BW 15 and 30 min after the first dose. No prophylactic vasopressor was used. During the first 40 min of anaesthesia a fluid load of 14 ml/kg BW was given i.v. If the mean arterial pressure (MAP) fell more than 20%, the infusion rate was increased. If the reduction in MAP exceeded 33% or if the systolic pressure decreased to less than 80 mmHg, patients were registered as haemodynamically unstable. In both groups the spinal anaesthesia caused a reduction in MAP. The MAP was lower in the fentanyl group than in the ketamine group at all times. In the fentanyl group six subjects developed a haemodynamically unstable condition, while only one subject in the ketamine group was registered as such (P less than 0.05). There was no significant change in heart rate in either group. We conclude that during spinal anaesthesia patients can in part be kept haemodynamically stable by intravenous administration of ketamine.     

Midazolam and diazepam in ketamine anaesthesia

Midazolam 0.07 mg/kg was compared with diazepam 0.12 mg/kg intravenously as an adjuvant to ketamine anaesthesia in healthy patients undergoing minor gynaecological operations of less than 15 minutes duration. The occurrence of induction and emergence sequelae, and patient acceptance of the technique was assessed by means of a questionnaire. The incidence of unpleasant dreams was 6.7% with midazolam and 26.7% with diazepam. There was no significant difference in any other sequelae. Overall patient acceptance was high at 96.7%.