Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--7. Effects on natural killer cell activity

Twenty four patients who underwent ophthalmic surgery were studied to evaluate activities of natural killer (NK) cells during and following total intravenous anesthesia with droperidol, fentanyl and ketamine. They were divided into three equal groups according to anesthetic methods employed. In enflurane group, anesthesia was induced with thiopental 5 mg.kg-1 and succinylcholine 1 mg.kg-1, and maintained with 1-2% enflurane, nitrous oxide (50%) and oxygen (50%). In original NLA group, anesthesia was induced as above and maintained with droperidol 0.15 mg.kg-1, fentanyl 5-10 micrograms.kg-1, nitrous oxide (70%) and oxygen (30%). The patients of total intravenous anesthesia group received droperidol 0.15 mg.kg-1, ketamine 2 mg.kg-1 and succinyl-choline 1 mg.kg-1 for induction of anesthesia, and then were given fentanyl 5-15 micrograms.kg-1, ketamine 2 mg.kg-1.hr-1 and oxygen (30%) for the maintenance of anesthesia. Vecuronium was given to every patient of the three groups for intraoperative muscle relaxation. Hartmann's solution was used at a speed of 5 ml.kg-1.hr-1. Peripheral venous blood 10 ml was drawn on six occasions during and after the surgery for the measurement of NK cell activities and endocrine response as judged by plasma catecholamine and cortisol levels. NK cell activities decreased significantly on the first post-operative day in enflurane group, but no significant differences were found among three groups in NK cell activities. The data suggest that inhaled anesthetics should not be easily employed for patients with depressed immune response, malignant disease and prolonged surgery.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--12. Effects on plasma complement and immunoglobulin concentrations]

Complements and immunoglobulins in the plasma are the important humoral factors to maintain immunity. As there is no study on immune response to total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK), twelve patients who underwent abdominal, neck dissection, or plastic surgery were studied to determine plasma concentrations of complements and immunoglobulins. In five patients of isoflurane group, anesthesia was induced with intravenous thiopental 5 mg.kg-1 and succinylcholine 0.8-1 mg.kg-1 and maintained with 1-2% isoflurane in nitrous oxide (50%) and oxygen (50%). The remaining seven patients of the DFK group received intravenous droperidol 0.25 mg.kg-1, fentanyl 1-2 micrograms.kg-1, ketamine 1-1.5 mg.kg-1 and succinylcholine 0.8-1 mg.kg-1 for the induction of anesthesia, and then they were given a total dose of fentanyl 5-15 micrograms.kg-1, ketamine 2 mg.kg-1.hr-1 and oxygen (30%) for the maintenance of anesthesia. Vecuronium was given intravenously as needed. Lactated Ringer's solution was used for intraoperative fluid replacement. A total of 40 ml of arterial blood was drawn on four occasions, just before the induction of anesthesia, at the recovery from anesthesia, on the third and tenth post-operative days. Plasma concentrations of complements (C3.C4) and immunoglobulins (IgG.IgA.IgM.IgD) were measured by immuno-turbidimetry. C3 concentrations in the plasma decreased significantly when the patients recovered from anesthesia, but they increased significantly on the third and tenth post-operative days in the isoflurane group. In the DFK group, they increased significantly on the tenth post-operative day only. No significant difference in the C3 concentrations was detected between two groups at any time of measurement.(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinical study of total intravenous anesthesia by using mainly propofol,fentanyl and ketamine--with special reference to its safety based on 26,079 cases

During a period of five years from January 1996 through December 2000 total intravenous anesthesia with mainly propofol, fentanyl and ketamine was administered to 26,079 patients including cardiac and neurosurgical patients at the University of Hirosaki Hospital and five other affiliated hospitals. The patients studied ranged from 1 year 8 months to 93 years in age, 9.2 kg to 135.0 kg in body weight and from 18 min to 22 hours 50 min in anesthetic time. With adequate monitoring, fentanyl 1-2 micrograms.kg-1 was given at first, then total-dose of ketamine 1 mg.kg-1 and propofol 1-2 mg.kg-1 were administered for the induction of anesthesia in adult patients. A total dose of fentanyl 3-15 micrograms.kg-1 was given combined with propofol 5-10 mg.kg-1 and ketamine 0.3-1.0 mg.kg.h-1. In craniotomy patients, ketamine was excluded. For pediatric patients, sevoflurane anesthesia was employed to establish i.v. route, and intravenous agents were given almost same as in the same manner as in adult patients. None of them developed either cardiac arrest or severe cardiovascular insufficiencies due to anesthesia alone. Their postoperative hepatic and renal functions evaluated by various biochemical indices and urine output were adequately maintained during anesthesia and for a week postoperatively. They were followed up to 3 months postoperatively only to fail to detect any adverse events related directly to this method of anesthesia. These data suggest that total intravenous anesthesia with propofol, fentanyl and ketamine has a very wide margin of safety.     

Total intravenous anesthesia for two patients complicated with myotonic dystrophy

Total intravenous anesthesia with propofol, fentanyl and ketamine (PFK) was given to two patients complicated with myotonic dystrophy. Case-1: A 42-year-old female underwent a hemithyroidectomy. Anesthesia was induced slowly with intravenous ketamine 20 mg and propofol 60 mg. Her tracheal intubation was performed smoothly without any muscle relaxants. Anesthesia was maintained with propofol infusion of 5 mg.kg-1.h-1, ketamine infusion of 0.3 mg.kg-1.h-1 and fentanyl 200 micrograms in total. She regained consciousness 20 minutes after the end of propofol infusion, and 15 minutes later, her trachea was extubated without any troubles. Case-2: A 41-year-old female underwent a removal of left parotid tumor. Anesthesia was induced slowly with ketamine 40 mg and propofol 100 mg intravenously. Anesthesia was maintained with propofol infusion of 5-10 mg.kg-1.h-1, ketamine infusion of 0.5 mg.kg-1.h-1 and fentanyl 350 micrograms in total. No muscle relaxant was used through the surgical procedure. Emergence from anesthesia was observed 10 minutes after the end of propofol infusion and her trachea was extubated. When a nasogastric tube was pulled out, her respiration stopped suddenly and she was intubated again only for two hours without any troubles. In both cases their serum CPK levels and rectal temperatures were very stable. PFK method would be a choice for patients with myotonic dystrophy.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine. 14. Effect on epidural pressure]

We studied effect of total intravenous anesthesia using ketamine, fentanyl and droperidol (DFK) on epidural pressure as an index for cerebrospinal fluid pressure in six surgical patients who underwent gastrectomy. The epidural catheter was inserted on the previous day. The epidural puncture was made at Th7-12 and the tip of the catheter was located 5 cm cephalad. The epidural pressure was measured before, just after and 30 minutes after the induction. The induction dose of fentanyl was 5 micrograms.kg-1 and that of ketamine was 1 mg.kg-1. The epidural pressure at the induction decreased in significantly by 19% as compared with that before the induction. The result suggested that DFK would not increase cerebrospinal fluid pressure when the doses of ketamine and fentanyl were changed.     

The effects of intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron in human: an F-wave study

We have investigated the effects of various intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron using an F-wave analysis in a total of 28 patients. All patients were divided randomly into three groups as follows; 2 mg.kg-1 intravenous bolus injection followed by 6 mg.kg-1.h-1 infusion of propofol (P group), 1 mg.kg-1 intravenous bolus injection followed by 1 mg.kg-1.h-1 infusion of ketamine (K group), and 5 micrograms.kg-1 injection of fentanyl (F group). The F-wave was determined after supramaximal electrostimulation of the median nerve in distal point. After establishing stable baseline values, intravenous injection of one of the three anesthetics was applied. The F-wave was recorded 3 minutes after the time of bolus administration. We found a significant (P = 0.018) reduction of the persistence from 77.5 +/- 15.2 to 40.9 +/- 16.8% in the propofol group. On the other hand, no significant changes in F-wave parameters were found in ketamine, or fentanyl group. These results suggested that motoneuron excitability in spinal cord could be inhibited by anesthetic dose of propofol, but not by ketamine or fentanyl.     

Continuous total intravenous anesthesia is useful for postoperative pain management

We compared postoperative pain in two groups. All anesthetic agents were continuously administered intravenously in a continuous PKF (propofol 2-10 mg.kg-1.h-1, ketamine 240 micrograms.kg-1.h-1 and fentanyl 0.4 microgram.kg-1.h-1) group. In a control group, anesthesia was maintained by GOI (N2O-oxygen-isoflurane). Twenty-two patients scheduled for gynecological lower abdominal surgeries were divided into the continuous PKF group (n = 11) and the GOI group (n = 11). Epidural anesthesia was employed in both groups, using local anesthetic agents and fentanyl during surgeries and for 24 hrs postoperatively. To evaluate pain, VAS and Prince Henry Score on rest, cough and movement were taken 2 hrs and 5 hrs postoperatively, and in the morning and afternoon of the 1st as well as 2nd postoperative days. The continuous PKF group showed lower scores than the GOI group. It is a great advantage to use continuous PKF for postoperative pain management, and our data indicate that low dose ketamine may induce pre-emptive analgesia.     

Cardiovascular effects of, and catecholamine response to, high dose fentanyl or NLA in patients for valve replacement]

We measured the cardiovascular effect of, and catecholamine and other hormonal responses to, anesthetic doses of fentanyl and original NLA in 25 patients for open heart surgery. The patients were randomly divided into three groups (group N, F30, F75). During induction, in group N; droperidol 0.25 mg.kg-1 and fentanyl 5 micrograms.kg-1, in group F30; fentanyl 30 micrograms.kg-1, and in group F75; fentanyl 75 micrograms.kg-1 were administered intravenously. Additional fentanyl was administered at a rate of 100 to 200 micrograms.h-1. Droperidol 0.25 mg.kg-1 was administered in group N when cardiopulmonary bypass (CPB) was disconnected. Plasma samples were assayed for norepinephrine, epinephrine, ACTH and cortisol before and after induction, during sternotomy, 60 minutes after institution of CPB, after weaning from CPB, and before as well as after extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and rate pressure product (RPP) were calculated simultaneously at the blood samplings. In all groups, no remarkable change in cardiovascular dynamics was observed. CPB was associated with marked increases in catecholamines, but high dose fentanyl in dose of 75 micrograms.kg-1 was able to suppress epinephrine level more than in group N. In high dose fentanyl group (F30, F75) ACTH was within normal ranges, even during CPB. The results suggest that high dose fentanyl is a complete anesthetic in patients for cardiac surgery. But a large dose of fentanyl causes small decreases in heart rate and arterial blood pressure. Our data indicate that group F30 is an attractive anesthetic technique for patients with valvular disease.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--10. Effects of prostaglandin E1 on the hepatic and renal functions following prolonged surgery under total intravenous anesthesia]

Twenty one patients who underwent prolonged surgical procedures over 10 hours under total intravenous anesthesia with droperidol, fentanyl and ketamine were studied to evaluate post-operative hepatic and renal functions as judged by serum levels of GOT, GPT, BUN and creatinine. They were divided into two groups. Ten patients of the PGE1 group were given PGE1 at a rate of 0.035 micrograms.kg-1.min-1 during anesthesia, and the remaining eleven of the control group were not given PGE1. The two groups were comparable concerning, age, body weight, height, operation time and anesthesia time. In the PGE1 group, significantly more intraoperative fluid was given than in the control group. The blood loss was more but insignificantly in the PGE1 group than in the control group. There was no significant difference in urine output and the amount of blood transfused between the two groups. In both groups, post-operative s-GOT and s-GPT levels were increased significantly compared with pre-operative values, but there was no significant difference between the two groups. Serum BUN levels of the 7-10 the post-operative days were increased significantly in the PGE1 group, but those of the control group were not. These data suggest that our method of total intravenous anesthesia with droperidol, fentanyl and ketamine, when applied even for prolonged surgical procedure over 10 hours, would have beneficial effects on the post-operative hepatic and renal functions.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--4. Control of intraoperative hypertension with nicardipine

Intraoperative hypertension over 160 mmHg systolic observed during total intravenous anesthesia with droperidol, fentanyl and ketamine was treated with intravenous nicardipine in 50 surgical patients. Nicardipine was given intravenously in a bolus of either 0.5 mg or 1.0 mg to treat the intraoperative hypertension. Systolic and diastolic blood pressures decreased soon after administration of nicardipine without simultaneous sinus tachycardia. Thus rate pressure product was also reduced significantly. Neither preoperative hypertension, nor systolic blood pressure just before the administration of nicardipine had any significant relationship with hypotensive effect of intravenous nicardipine. We did not experience any adverse reaction with the drug. We conclude that intravenous nicardipine in a dose of 0.5-1.0mg can be given repeatedly to overcome hypertension observed during this method of anesthesia.     

A clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--2. Pharmacokinetics following the end of continuous ketamine infusion

Ten surgical patients who received various operative procedures including abdominal surgery and ENT surgery were the subjects of the pharmacokinetic study of total intravenous anesthesia with droperidol, fentanyl and ketamine. Six arterial samples were taken through an indwelling catheter in the left radial artery to measure plasma levels of ketamine and its metabolites by means of gas liquid chromatography. Two hours following the end of the ketamine infusion, plasma ketamine levels decreased to 14% of the control value (0.81 micrograms.ml-1), while metabolite I (K1) was still about 1.8 micrograms.ml-1 in the plasma. The control value of plasma ketamine just before the end of its infusion had not any significant relationship with the total dose of ketamine, total dose of fentanyl, blood loss or fluid given. The results of our study suggest that long continuous ketamine infusion would be safe as judged by its pharmacokinetics.     

Anesthesia with high dosage fentanyl in coronary patients: effects of pretreatment with droperidol and diazepam]

The Authors have considered the effects of droperidol or diazepam treatments in patients undergoing high-dose fentanyl anesthesia in cardiac surgery. Twenty patients have been examined and divided in two groups: group A received droperidol (0.2 mg.kg-1) and group B diazepam (0.1 mg.kg-1) five minutes after fentanyl anesthesia induction (500 micrograms.min-1) to reach the "sleep dose". The diazepam pretreatment, as regards droperidol, reduces a dose of fentanyl necessary to obtain the conscience loss (21.5 +/- 2.5 micrograms.kg-1 vs 28 +/- 2.9 micrograms.kg-1). Hemodynamically the droperidol group is very stable, whereas the diazepam group shows certain myocardial depression and less protection at the OTI time.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--9. Control of intraoperative hypertension with diltiazem

Intraoperative hypertension over 160 mmHg systolic and sinus tachycardia over 100 bpm are often observed during total intravenous anesthesia with droperidol, fentanyl and ketamine. Fifty-seven surgical patients who developed hypertension over 160 mmHg systolic during various operative procedures under this type of anesthesia were given diltiazem intravenously to overcome the situation. Their blood pressure and heart rate decreased soon after the administration of diltiazem. The rate pressure product was reduced significantly. Neither preoperative hypertension nor difference of doses between 5 mg and 10 mg of diltiazem had any significant relationship with hypotensive effect of intravenous diltiazem. But the higher the systolic-pressure was just before the administration of diltiazem, the more effective diltiazem was. No adverse effects with this drug was observed. We can conclude that intravenous diltiazem in a dose of 5 mg or 10 mg may be repeatedly given to overcome hypertension or sinus tachycardia during this type of anesthesia without any adverse effects.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--15. Application for cardiac anesthesia]

Total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) was administered to 36 cardiac patients who underwent mostly coronary artery bypass graft or heart valve replacement. The induction and maintenance of anesthesia using this technique were almost satisfactory with little decrease in systolic blood pressure (SBP), although six patients among the early 21 patients developed hypotension below 90 mmHg (SBP) during the induction, and required vasopressors. Half of the patients had hypertensive episode of above 180 mmHg (SBP), from the start of operation to onset of cardiopulmonary bypass, which was safely and effectively overcome by a small dose of antihypertensive agents. Total intravenous anesthesia with DFK was accompanied with much more hypertensive episodes compared to anesthesia with moderate dose fentanyl (30 micrograms.kg-1) combined with enflurane. However, the incidence of cardiovascular complications following anesthesia was not statistically different between the two anesthesia groups. In addition, most of the patients with DFK showed a rapid awaking time with relatively good postoperative cardiovascular stability. These findings suggest that total intravenous anesthesia with DFK is accompanied with minimal hemodynamic changes during and after open heart surgery.     

Nitroglycerin reduces requirement of pancuronium in surgical patients

We performed a study on 34 adult surgical patients between 15 and 56 years of age, to evaluate whether synergism between nitroglycerin and pancuronium exists or not. Neuromuscular (NM) transmission was measured by electromyography of the thenar muscle using transcutaneous electrodes. Anesthesia was induced by droperidol 0.2 mg.kg-1, fentanyl 50 micrograms, thiamylal 150-250 mg, and succinylcholine 1 mg.kg-1, and maintained with nitrous oxide and O2 (67:33) supplemented with repeated i.v. doses of fentanyl (within 15 micrograms.kg-1). Pancuronium 4 mg was given at the 20% recovery from succinylcholine induced NM block. Sequential i.v. doses of pancuronium 1 mg were injected repeatedly at the every 20% recovery until the end of operation. To control blood pressure, nitroglycerin, ranging from 0 to 5 micrograms.kg-1.min-1, was given intravenously. The linear multiple regression analysis was performed between the dose of pancuronium (micrograms.kg-1.hr-1) and the dose of nitroglycerin (micrograms.kg-1.min-1), the age, sex, or body weight of the patients. The results show that the dose of pancuronium decreases with increasing dose of nitroglycerin. No relationship was found between the dose of pancuronium and the age, sex, or body weight of the patients. In conclusion, nitroglycerin reduces requirement of pancuronium in surgical patients.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl, and ketamine--6. Effects on postoperative liver function

We have developed a new method of total intravenous anesthesia with droperidol, fentanyl, and ketamine, and have administered it to more than 700 surgical patients. We studied whether this method of anesthesia would influence postoperative liver function or not. A total of sixty elective surgical patients were the subjects of this study. Thirty patients underwent total hysterectomy under either the total intravenous anesthesia (15 patients) or modified neurolept-anesthesia with pentazocine (15 patients). The remaining 30 patients underwent gastrectomy under either this total intravenous anesthesia (15 patients) or enflurane-N2O anesthesia (15 patients). The hepatic function was evaluated as judged by s-GOT, s-GPT, ALP, gamma-GPT and total bilirubin levels, before anesthesia and during the first to third postoperative day. The patients for gastrectomy under enflurane-N2O anesthesia had significantly increased postoperative gamma-GPT levels compared with the patients of total intravenous anesthesia. Any other variables showed no significant difference among groups. We consider that this method of total intravenous anesthesia has no adverse effects on postoperative liver function as compared with other usual anesthetic methods.     

Target-controlled propofol infusion for general anesthesia in three obese patients

We report three cases in which the target-controlled propofol infusion technique was used in obese patients for general anesthesia. General anesthesia was induced by intravenous administration of fentanyl 150-300 micrograms and ketamine 50-80 mg and propofol 2 micrograms.ml-1 to achieve a target blood concentration by target-controlled infusion system. Anesthetic maintenance was achieved by ketamine 1 mg.kg-1.h-1 for 1 hour after the induction, propofol at target blood concentration of 2-3.5 micrograms.ml-1 and the intermittent epidural injection of 1.5% lidocaine through an epidural catheter. The surgical procedures were uneventful. The estimated blood concentrations of propofol at emergence from anesthesia calculated by ConGrace ranged from 1.49-1.69 micrograms.ml-1, and it took 230-300 seconds to emerge from anesthesia. The target-controlled propofol infusion technique appears useful to control the depth of anesthesia in obese patients.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--3. Pharmacokinetics during prolonged continuous ketamine infusion

A simple and precise method has been developed for the analysis of plasma ketamine and its metabolites using gas chromatography with flame ionization detection after elution by trifluoroacetic dehydride. Seven surgical patients who received total intravenous anesthesia with droperidol, fentanyl and ketamine anesthesia over 5 hours were the subjects of the study. During the anesthesia, ketamine levels were from 1.0 to 2.0 micrograms.ml-1. After the termination of ketamine infusion, their levels decreased gradually. Metabolites I levels were elevated gradually to about twofold of that of ketamine and remained high. Metabolite II was detected in only two patients and their levels were under 0.2 micrograms.ml-1. The results of our study suggest that this type of anesthesia of prolonged duration is safe as judged by the present pharmacokinetic study.     

Anesthetic management of an emergency surgery for panperitonitis during an asthmatic attack

We report anesthetic management of an emergency surgery for panperitonitis during an asthmatic attack in a patient with angina pectoris. A 71-year-old male patient, complaining of abdominal pain and dyspnea, was diagnosed as having panperitonitis and asthmatic attack by surgeons in the emergency room. General anesthesia was induced by intravenous injection of propofol (30 mg), ketamine (30 mg), fentanyl (200 micrograms), suxamethonium (60 mg) and diltiazem (5 mg) following cannulation of the left radial artery for continuous monitoring of direct arterial pressure. Anesthesia was maintained by continuous infusion of propofol (4-10 mg.kg-1.h-1) and ketamine (1 mg.kg-1.h-1) in combination with intermittent epidural injection of local anesthetics. Although sudden onset of increased peak airway pressure occurred 45 minutes after starting operation, 50 mg of propofol injection and 500 mg of aminophyline infusion could relieve this high airway pressure. Because increased peak airway pressure appeared frequently and this could not be relieved by bolus injection of propofol, we changed the intravenous anesthesia to nitrous oxide-oxygen-isoflurane (GOI). After this change, no asthmatic attack occurred during the operation. While the mechanical ventilation was required during the early postoperative period along with infusion of aminophyline and inhalation of beta-stimulants, the patient was weaned successfully from the mechanical ventilation 12 hours postoperatively. It was speculated that the intraoperative asthmatic attack might have been caused by light level of anesthesia with propofol and ketamine. We concluded that other analgesics, such as fentanyl or epidural local anesthetics, must have been supplemented at proper timing during the continuous infusion of propofol and ketamine during the surgery.     

小剂量氯胺酮对体外循环促炎细胞因子反应及心肌损伤的影响

目的 探讨小剂量氯胺酮对体外循环（CPB）诱发的促炎细胞因子反应及心肌损伤的影响。方法 20例择期瓣膜替换术病人,随机分成氯胺酮组（n＝10）和对照组（n＝10）。氯胺酮组于麻醉诱导和转流开始时按1mg.kg^-1静注氯胺酮,对照组则采用等量生理盐水注射。分别于术前（T1）、CPB60min（T2）、CPB结束后2h（T3)、4h(T4)及24h（T5）各时间点测定动脉血中下列各项指标;肿瘤坏死因子－α（TNF－α）、白细胞介素－6（IL－6）、白细胞介素－8（IL－8）、血浆过氧化脂质（LPO）、心肌肌酸酶同工酶（CK－MB）。结果 与术前（T1）比较,两组TNF－α、IL－6、IL－8、LPO、CK－MB均明显升高（P＜0．05或0．01）;但氯胺酮组T2－T5TNF－α、IL－6、IL－8浓度、T3LPO浓度和T3、T4、CK－MB活性均显著低于对照组（P＜0．05）。结论 小剂量氯胺酮能有效抑制CPB诱发的促炎细胞因子反应和心肌损伤。