STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA XXII: PHENOPERIDINE AND FENTANYL, ALONE AND IN COMBINATION WITH DROPERIDOL

An assessment of the general properties of fentanyl and phenoperidinehas been made by including them in the continuing trial of drugsgiven before anaesthesia. Fentanyl and phenoperidine both differedfrom morphine in that they produced much less sedation, whilethe incidence of restlessness was greater after fentanyl thanit was with morphine or phenoperidine. None of the drugs hadany remarkable effect on cardiovascular system stability, althoughboth fentanyl and phenoperidine were associated with a notableincidence of tachycardia. Neither drug showed as strong an emeticeffect as did morphine, phenoperidine causing the least sicknesswhile fentanyl occupied an intermediate position. The effectof addition of droperidol to fentanyl and phenoperidine wasto increase the sedative effect over that of either drug givenalone, whilst the unpleasant subjective effects and restlessnessassociated with droperidol given alone were also reduced bycombination with the opiates. The anti-emetic effect of droperidolwas confirmed. Present address: Department of Anesthesiology, The Mayo Qinic,Rochester, Minnesota 55901, U.S.A     

Postoperative nausea and vomiting after laparoscopic cholecystectomy under total intravenous anesthesia using propofol combined with fentanyl or pentazocine

BACKGROUND: The aim of this study was to compare the incidence of postoperative nausea and vomiting (PONV) in propofol-anesthetized patients receiving either fentanyl or pentazocine as opioid supplement. METHODS: Sixty-seven patients scheduled for laparoscopic cholecystectomy were analyzed retrospectively. Patients were classified into two groups according to opioid supplement under propofol-anesthesia; pentazocine group (n = 26) and fentanyl group (n = 41). Anesthesia was induced with propofol using target controlled infusion method, and was maintained with propofol infusion with pentazocine or fentanyl and intermittent administration of vecuronium with 40% oxygen in air. RESULTS: The incidence of PONV was 23.1% in fentanyl group and 22.0% in pentazocine group, respectively. The incidence of PONV was not different between the groups. There were no severe complications. CONCLUSIONS: The incidence of PONV in propofol-anesthetized patients receiving pentazocine as opioid supplement is not different from that in patients receiving fentanyl.     

A DOUBLE-BLEND CONTROLLED STUDY OF THE EFFECTS ON RESPIRATION OF PENTAZOCINE, PHENOPERIDINE AND MORPHINE IN NORMAL MAN

Three drugs and saline were given intravenously, on separateoccasions, to eight normal subjects. The doses used were pentazocine20 mg, phenoperidine 1.5 mg and morphine sulphate 10 mg, eachper 70 kg body weight End-tidal Pco₂ and ventilatory patternwere followed continuously; expired volume and oxygen consumptionwere measured before and at intervals after injection; a rebreathingcarbon-dioxide response test was also applied. The three drugsproduced similar, and significant increases, of the order of5 torr in Pco₂ and dissimilar, significant, reductions in ventilationwhich could be related to dissimilar effects on oxygen consumption:injection of morphine or of phenoperidine was followed within10 minutes by an average reduction in oxygen consumption by20–30 per cent whereas after pentazocine the reductionwas only about 10 per cent. The rises in Pco₂ provided a guideto respiratory depression which was as consistent and as statisticallysignificant as most quoted changes in parameters of carbon-dioxideresponse tests. The results of the carbon dioxide-response testused in this trial were very variable.     

ALTERATIONS IN RESPONSE TO SOMATIC PAIN ASSOCIATED WITH ANAESTHESIA XIX: STUDIES WITH THE DRUGS USED IN NEUROLEPTANAESTHESIA

The effects of some intravenously administered drugs on sensitivityto tibial pressure-induced somatic pain were investigated ina controlled, double-blind trial. The drugs included those commonlyemployed in neuroleptanaesthesia (fentanyl, phenoperidine anddroperidol), standard opiates (morphine, diamorphine), and astandard tranquillizer (diazepam). The analgesics were givenin what are commonly regarded as clinically equipotent dosages.Fentanyl and phenoperidine decreased the subjects' sensitivityto somatic pain, whilst saline, morphine, diamorphine and diazepamdid not have any effect. Droperidol caused an increase in sensitivity,and the addition of droperidol to either phenoperidine or fentanylwas associated with a simple summation of effect. It was concludedthat there is a difference in the mode of action of fentanyland phenoperidine in comparison to morphine, the former havinga relatively greater effect on the perceptual mechanisms ofpain and the latter a relatively greater effect on the affectiveexperience of pain. Present address: Department of Anesthesiology, The Mayo Clinic,Rochester, Minnesota 55901, U.S-A.     

Comparison of pentazocine and fentanyl in total intravenous anesthesia using propofol

BACKGROUND: Pentazocine may be an alternative for fentanyl during total intravenous anesthesia (TIVA) using propofol. The authors compared the efficacy and safety of pentazocine for analgesics in TIVA using propofol. METHODS: Eighty-nine patients scheduled for mastectomy were analyzed retrospectively. Patients were classified into two groups by used analgesics; pentazocine (Group P, n = 34) and fentanyl (Group F, n = 55). Anesthesia was induced with propofol, using target controlled infusion method, and ketamine 20-50 mg, and was maintained with propofol infusion and increments of fentanyl or single dose of pentazocine with 40% oxygen in air. Postoperative pain was assessed using a visual analogue pain scale (VAS). RESULTS: There were no differences in the patient background between both groups. Systolic as well as diastolic blood pressure and heart rate were not different between both groups during surgery. The maintenance dose of propofol was not different between the two groups. Awakening time in about 80% of patients was within 15 minutes and is not different between the two groups. There were no differences between the two groups regarding VAS. There are no severe complications. Incidence of nausea and vomiting was not different between the two groups. CONCLUSIONS: The results suggest that pentazocine would provide a stable hemodynamic state, rapid recovery and an effective postoperative pain relief to the same degree as with fentanyl in TIVA with propofol.     

Comparison of nalbuphine and pentazocine in the treatment of postoperative pain by self-administration

The side-effects of two opioid agonist-antagonists, nalbuphine and pentazocine, were assessed when used for patient-controlled postoperative analgesia. Forty ASA I or II patients scheduled for upper abdominal surgery were randomly allocated to two equal groups. The anaesthetic technique was the same for all the patients: premedication with atropine and diazepam, induction with thiopentone and suxamethonium and maintenance with fentanyl, pancuronium, nitrous oxide and halothane. Patient-controlled computer assisted analgesia (On-Demand Analgesia Computer) was started in the recovery room at least 2 h after the last administration of fentanyl. The parameters used were: a routine hourly dose (the half of that received during the previous hour), with on demand delivery of nalbuphine (15 micrograms.kg-1) or pentazocine (45 micrograms.kg-1) aliquots respectively, with a refractory period between two demands of 4 min and a total hourly maximum dose of 16 mg and 48 mg respectively. The following parameters were measured before the start of self-administration, and every hour afterwards for 24 h: systolic (Pasys) and diastolic blood pressures, heart rate, pressure-rate product (PRP), respiratory rate, end-tidal CO2 and pain (by way of a three point scale). Analgesia was assessed on a four-point scale every 6 h. The total doses of nalbuphine and pentazocine administered were 94 +/- 43 mg and 251 +/- 150 mg respectively. The only parameters significantly different between the two groups were Pasys and PRP, being higher in the pentazocine group. There were no significant differences in the side-effects (drowsiness, nausea, vomiting, headache, amnesia, logorrhoea and urine retention). All patients in both groups were satisfied with this technique.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Antagonist Effect of Naloxone Hydrochloride after Neuroleptanaesthesia during Neurosurgery

The effects of naloxone were studied in 82 patients undergoing intracranial surgery under general anaesthesia with fentanyl or phenoperidine. After the operation was finished the patients' alertness, sensitivity to pain, blood pressure, pulse rate, respiratory rate, tidal and minute volume were recorded parallel with arterial blood gas analyses prior to and immediately after the administration of varying amounts of naloxone i.v. in a single dose. These parameters were also repeatedly controlled for several hours in the postoperative period.
The results show that a single i.v. naloxone dose of 1 μg/kg b.w. is effective in the rapid and definite reversal of the respiratory depression caused by the analgesics. This dose was neither correlated to the total amount of analgesics given, nor to the time period which elapsed between the last dose of the analgesic drug and the administration of naloxone. No side effects or complications were encountered when the indicated doses of naloxone were given. It is concluded that, even in a small single dose, naloxone effectively antagonises the respiratory depression caused by fentanyl and phenoperidine without totally eliminating the immediate postoperative analgesic effects of these agents.     

A COMPARISON OF THE CIRCULATORY EFFECTS IN MAN OF THE ANALGESICS FENTANYL, PENTAZOCINE AND PETHIDINE

The cardiovascular responses to five sequential intravenousinjections of pentazocine (5x0.6 mg/kg), fentanyl (5x0.001 mg/kg)and pethidine (5x1.0 mg/kg) were assessed in conscious and anaesthetizedsubjects. In conscious volunteers pentazocine raised the systolicpressure by 30 per cent. Pentazocine and pethidine raised thediastolic pressure by 10 per cent and the heart rate by 15 percent; with pethidine the increases were not sustained but tendedto fluctuate. Fentanyl did not affect the pressure or heartrate. In anaesthetized patients, all three analgesics causeda 20–25 per cent fall in blood pressure and heart rate,fluctuations in pressures occurring in the pentazocine and pethidinegroup. No changes of e.c.g. pattern were observed. Pentazocine,pethidine and fentanyl thus exert different haemodynamic effectsin conscious and anaesthetized subjects. A summary of this paper was presented at the Pain Symposiumheld in Munich, October 17-19, 1969.     

SUPPLEMENTATION OF GENERAL ANAESTHESIA WITH NARCOTIC ANALGESICS

Four analgesic drugs—fentanyl, phenoperidine, morphineand pethidine—were compared in a double-blind trial involving113 patients paralysed and ventilated with nitrous oxide andoxygen. The differences between the drugs were relatively small.There were only slight differences in "duration of action ",a term which is questioned in this context. Pethidine appearedto have a slightly longer duration of action than the otherdrugs. The problems inherent in studying analgesics in thismanner are discussed.     

A COMPARISON OF POSTOPERATIVE ACID-BASE EQUILIBRIUM AND RESPIRATORY ADEQUACY AFTER TWO TYPES OF NEUROLEPTANALGESIA

Two different types of neuroleptanalgesia supplemented withnitrous oxide and oxygen, NLA I (haloperidol and phenoperidine)and NLA II (dehydrobenzperidol and fentanyl), were given totwenty-seven and thirty-six patients, respectively. The comparisonof respiratory adequacy shows that, after NLA I, there was respiratoryacidosis and slight metabolic acidosis, most prominent 30 minutesafter anaesthesia with a tendency to return to normal duringthe three-hour follow-up period. With NLA II there were no signsof respiratory depression. Base excess and pH also remainedwell within the physiological range.     

CONTROLLED COMPARISON OF I.M. MORPHINE AND BUPRENORPHINE FOR ANALGESIA AFTER ABDOMINAL SURGERY

In a double-blind randomized non-crossover trial 47 patientsreceived either morphine or buprenorphine by regular 1.m. injectionfor 24 h after abdominal surgery. The two drugs were equallyeffective as analgesics at the doses used Five in the buprenorphinegroup and none in the morphine group were excluded because ofrespiratory depression Four of these had received opiates duringoperation The remainder of the buprenorphine group developedprogressively slower respiration rates after 12 h The resultsindicate that buprenorphine has a synergistic respiratory depressioneffect with fentanyl and phenoperidine and may have a cumulativeeffect when given regularly on a 6-hourly regimen     

Pentazocine increases bispectral index without surgical stimulation during nitrous oxide–sevoflurane anesthesia

Although there have been a large number of reports on the effects of opioids on the bispectral index (BIS) during anesthesia, the effects of pentazocine on the BIS have not been reported. In this study, 60 patients scheduled for elective oral surgery [30 females, 30 males; all American Society of Anesthesiologists Physical Status (ASA PS) category 1] were enrolled in the trials. Maintaining gender parity, we randomly assigned the patients to one of three groups: pentazocine group (0.3 mg/kg; n = 20), fentanyl group (1 μg/kg; n = 20), or saline group (n = 20); these opioids were administered intravenously 15 min after the intubation. Anesthesia was induced with thiopental and vecuronium bromide and maintained with nitrous oxide (4 l/min)–oxygen (2 l/min)–sevoflurane (1%). At 15 min after the intubation, mean arterial blood pressure (MAP), heart rate (HR), and BIS index were recorded as baseline values. MAP, HR, and BIS values were measured at 2.5-min after the intubation up to 30 min. All data were expressed as the mean ± standard deviation. Differences in BIS values, MAP, and HR among the three groups throughout the experiment were analyzed using two-way repeated-measures analysis of variance (ANOVA), and demographic data among the three groups were analyzed using one-way ANOVA. Post hoc comparisons were performed using Fisher’s protected least significant difference test. A P value of <0.05 was considered to indicate statistically significance. MAP and HR showed no significant differences among the three groups during the study. BIS values significantly increased between 5 and 15 min after the intubation relative to the baseline value in the pentazocine group (P < 0.001), and BIS values in this group were significantly during this time period than those in the fentanyl and saline group (P < 0.001). BIS values were not significantly different between the fentanyl group and saline group. These results indicated that pentazocine, but not fentanyl, under nitrous oxide–sevoflurane anesthesia caused a statistically significant increase in BIS in our patients.     

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.     

The absence of teratogenic effects of some analgesics used in anaesthesia

The possibility exists that agents used in anaesthesia may have adverse teratogenic effects on staff, patients, and developing fetuses. It has been shown that a range of neurotropic drugs, when injected into pregnant mice on the 9th day of gestation, produce a characteristic group of central nervous system malformations in their fetuses. We have studied the possible teratogenicity of pethidine, fentanyl, phenoperidine and lignocaine when tested in this way and conclude that they appear to have less effect than other neurotropic drugs previously tested.     

Continuous intravenous administration of fentanyl reduces tenesmus after transurethral resection of the prostate (TUR-P)

BACKGROUND: The relief from tenesmus is important after transurethral resection of the prostate (TUR-P). We evaluated the effect of continuous intravenous administration of fentanyl on the tenesmus. METHODS: Eleven patients receiving fentanyl infusion (fentanyl group) were compared with fourteen patients without fentanyl infusion (control group) retrospectively. All patients underwent TUR-P under spinal anesthesia with hyperbaric 0.5% bupivacaine 2.2-2.8 ml. In the fentanyl group, fentanyl infusion 25 microg x hr(-1) was started followed by fentanyl 50 microg administration postoperatively. RESULTS: In the fentanyl group, NSAIDs were needed in only one patient. Eleven patients in the control group, however, required NSAIDs and three of them needed additional pentazocine administration. The required amount of NSAIDs per patient was significantly smaller in the fentanyl group (Mann-Whitney U test, P < 0.01). In the fentanyl group, one patient had slight nausea but needed no care. Other side effects, such as respiratory depression, hypotension, bradycardia and somnolence were not observed. CONCLUSIONS: Continuous intravenous administration of fentanyl was very effective and safe enough for the tenesmus after TUR-EP.     

PLASMA CONCENTRATION AND METABOLISM OF PHENOPERIDINE IN MAN

The plasma concentrations of phenoperidine were measured infive patients during general anaesthesia. The concentrationof the drug decreased rapidly between 2 and 40 min and thendeclined more slowly. Detectable concentrations of phenoperidinewere present in plasma for at least 3 h. In the five patients,the distribution half-life of the drug ranged from 3.19 to 14.23min and the elimination half-life from 47.31 to 162.30 min.Unchanged phenoperidine and two identified metabolites (pethidineand norpethidine) were present in urine.     

THE INFLUENCE OF NEUROLEPTANALGESIC DRUGS ON CEREBROSPINAL FLUID PRESSURE

The effects of the neuroleptanalgesic drug combinations, droperidol5 mg+phnoperidine 1.5 mg, and droperidol 5 mg+fentanyl 0.1 mg,on the cerebrospinal fluid (c.s.f.) pressure, have been studiedin patients with normal c.s.f. pathways during controlled ventilation.The influence of droperidol 5 mg+fentanyl 0.1 mg on intracranialpressure has also been investigated in patients with intracranialspace-occupying lesions. In patients with normal c.s.f. pathways,droperidol and phenoperidine produced only small alterationsin c.s.f. pressure in either direction, while a significantdecrease in overall mean c.s.f. pressure. Similarly, in patientswith intracranial space-occupying lesions, droperidol plus fentanylproduced decreases in c.s.f. pressure in all but one of thecases studied. The striking difference between the effect onc.s.f. pressure of these drugs and of the volatile anaestheticagents could be of importance to the clinical anaesthetist dealingwith head injuries or working in a neurosurgical unit, whenunder conditions of controlled ventilation these drugs couldbe used as adjuvants to nitrous oxide-oxygen anaesthesia. ^*Present address: Department of Anaesthesia,University of Leeds.     

THE INFLUENCE OF DRUGS USED IN NEUROLEPTANALGESIA ON CARDIOVASCULAR AND VENTILATORY FUNCTION

The circulatory and ventilatory influences of various combinationsof the narcotic analgesics phenoperidine and fentanyl, and theneuroleptics haloperidol and dehydrobenzperidol, were investigatedduring nitrous oxide anaesthesia in 230 patients. Measurementsof cardiac output and other haemodynamic variables in nine patientssupported the general findings that the cardiovascular effectsof the analgesics were modified by alterations of ventilation,in particular the haemodynamic effects of concurrent hypercapnia.Serious circulatory disturbances were not found following premedicationwith neuroleptic drugs. Mechanisms of ventilatory depressionfollowing the use of the analgesics have been evaluated, andindices of ventilation and arterial oxygenation show that postoperativevalues after neuroleptanalgesia are comparable to those afterother methods of anaesthesia. The rationale of neuroleptanalgesiacombined with light general anaesthesia is explored and thepharmacology of the drugs is reviewed.     

Influence of flunitrazepam on body functions.

The effects of intravenous flunitrazepam (Rohypnol, Roche) on various body functions were studied and the following conclusions were reached: it is a very potent sedative/hypnotic even in small doses, it may cause depression of spontaneous breathing, it does not give rise to raised cerebrospinal fluid or intra-ocular pressure, it does not adversely affect renal function, and it can be used quite safely in combination with fentanyl or pentazocine in anaesthetic practice.     

EFFECT OF CERTAIN ANAESTHETIC AGENTS ON THE ACTIVITY OF RAT HEPATIC {delta}-AMINOLAEVULINATE SYNTHASE

The activity of -aminolaevulinic acid synthase (E.C. 2.3.1.37 [EC] )(the rate-limiting enzyme for haem and porphyrin biosynthesis)has been measured in the rat liver after the repeated administrationof anaesthetic agents in vivo. The activity of the enzyme wasincreased by Althesin, chlordiazepoxide, enflurane, etomidate,lignocaine, methohexitone, methoyflurane, pentazocine and thiopentoneand decreased by procaine. No significant changes in activityoccurred after the administration of amethocaine, atropine,bupivacaine, diazepam, droperidol, halothane, ketamine, morphine,nitrous oxide, pethidine, phenoperidine, prilocaine and propanidid.It is suggested that those anaesthetic agents which inducedactivity of the enzyme should not be administered to patientswith an acute porphyria.