Opioid supplementation to propofol anaesthesia for outpatient abortion: a comparison between alfentanil, fentanyl and placebo

One hundred and sixty-four patients scheduled for elective termination of pregnancy under general anaesthesia were randomly assigned to receive one of three different supplements to propofol and oxygen in nitrous oxide anaesthesia: 0.1 mg fentanyl, 0.5 mg alfentanil or placebo. Postoperative pain and nausea, as well as complications during anaesthesia were studied. There were no differences in complications or complaints by surgeons during anaesthesia, and no patient in any group reacted unsatisfactorily to surgery. The patients in the placebo group consumed significantly more propofol during the procedure (P less than 0.001). No differences were seen in time until hospital discharge between the three groups. Complaints about postoperative pain were significantly less frequent among patients receiving fentanyl (P less than 0.01). The number of patients requesting postoperative analgetics, however, did not differ. There was no difference in the frequency of nausea or vomiting, but postoperative pain was found significantly to increase complaints of nausea (P less than 0.01) and also time until hospital discharge (P less than 0.01). In conclusion, opioid supplementation lowered the amount of propofol needed for anaesthesia. Alfentanil 0.5 mg did not improve the postoperative course. Fentanyl 0.1 mg decreased the frequency of postoperative pain without increasing the time to hospital discharge.     

Pupil response to alfentanil and fentanyl

The pupillary response to alfentanil, fentanyl and a saline placebo was measured in patients anaesthetised in a standard manner with halothane, to determine whether the pupil diameters changed in a way which could be distinguished from background activity. Measurements were made to the nearest 0.1 mm using a purpose-built pupillometer. The response to the drugs can be clearly distinguished from the background activity seen in the placebo group. The time courses of constriction caused by the two drugs are significantly different from the placebo group responses. The time to maximum to response with alfentanil is 4 minutes compared with 8 minutes for fentanyl. Both drugs produced at least 35% reduction in mean pupil diameter compared with the placebo group. The duration of the response to alfentanil was 25 minutes, whereas the fentanyl response lasted more than one hour.     

Alfentanil infusions. Comparison of bolus administration of fentanyl with three alfentanil infusion regimens

Three different dosage regimens of alfentanil were compared with boluses of fentanyl in 80 patients who underwent a variety of surgical procedures. Alfentanil given by infusion at a rate of 7.5 micrograms/kg/minute for 10 minutes followed by 0.75 micrograms/kg/minute, was shown to provide a stable anesthetic which minimises the use of a volatile agent for surgery that lasts more than 45 minutes.     

Effects of fentanyl or alfentanil as supplement to propofol anaesthesia for termination of pregnancy

One hundred and twenty patients undergoing early legal termination of pregnancy by dilatation and suction curettage before 12 weeks of pregnancy were randomly allocated to receive total intravenous propofol anaesthesia either alone or supplemented with fentanyl 1.5 μg·kg^-1 or alfentanil 15 μg kg^-1. Supplementation with fentanyl or alfentanil improved operating conditions ( P <0.01), reduced total propofol requirements ( P < 0.01) and reduced postoperative pain intensity ( P < 0.05). Immediate recovery, assessed by the time patients took to open the eyes, to give correct date of birth and by co–operation score, was more rapid in the alfentanil group compared to the control group ( P < 0.05), whereas there was no significant difference between the alfentanil and fentanyl groups. The three anaesthetic techniques did not differ with regard to side effects.
In conclusion, total intravenous propofol anaesthesia in patients undergoing early termination of pregnancy was improved by supplementation with either fentanyl 1.5 μg kg^-1 or alfentanil 15 μg–kg^-1. The benefit was slightly greater with alfentanil than with fentanyl.     

Propofol and alfentanil total intravenous anaesthesia: a comparison of techniques for major thoracic surgery

Background : Previous work has highlighted the disadvantages of propofol as a sole agent for total intravenous anaesthesia (TIVA). This randomised study investigated three combinations of propofol and alfentanil as TIVA for major thoracic surgery.
Methods : In 73 patients undergoing elective thoracic surgery, anaesthesia was conducted either with sodium thiopentone induction and inhalational maintenance (incorporating isoflurane) or with TIVA using propofol with alfentanil (by infusion at one of two rates or in incremental doses). Vital signs and recovery characteristics were recorded.
Results : There were no significant differences in heart rate or blood pressure between groups during either induction or maintenance. Depth of anaesthesia was controlled satisfactorily in all groups. Recovery characteristics were similar between treatment groups, although there was a trend towards earlier orientation
Conclusion : Continuous infusions of propofol and alfentanil provide safe and reliable TIVA for major thoracic surgery. TIVA was found to be a satisfactory technique in more elderly patients than previously described. The higher of the two alfentanil infusion rates may result in a better combination of propofol and alfentanil with respect to recovery times than the lower.     

Analgesia for appendectomy: comparison of fentanyl and alfentanil in children

During etomidate-N2O vecuronium anaesthesia for appendectomy, three groups of 13 children received fentanyl as a 10 micrograms.kg-1 loading dose and 2 micrograms.kg-1 increments in Group F, alfentanil as a 100 micrograms.kg-1 initial loading dose and either 20 micrograms.kg-1 increments in Group AB or 1 microgram.kg-1.min-1 continuous infusion in Group AI. On the basis of intraoperative heart rate changes, the opioid regimen was less efficient in Group AB (P less than 0.05). Based upon equianalgesic cumulative dosage, the alfentanil/fentanyl potency ratio was in the range of 1/10 to 1/13. The awakening time was similar in all groups, as were the duration of postoperative analgesia, the incidence of postoperative pain and the incidence of nausea and vomiting. We conclude that high-dose alfentanil is as efficient as fentanyl for intra and postoperative analgesia in children undergoing appendectomy.     

Anaesthesia for short outpatient procedures. A comparison between thiopentone and propofol in combination with fentanyl or alfentanil

We studied supplementation of propofol or thiopentone anaesthesia with 0.5 or 1.0 mg alfentanil or 0.05 or 0.1 mg fentanyl for minor gynaecological outpatient procedures. Four hundred patients scheduled for elective termination of pregnancy were randomly allocated to one of eight groups. Induction agent doses, peroperative complications, complaints about pain and emesis during the postoperative period, and time to discharge were studied. Propofol compared to thiopentone was associated with a shorter time to discharge, 103±28 and 115±33 minutes respectively ( P <0.05) and anxiety during recovery was more frequent in the thiopentone group ( P <0.05). The need for postoperative reserve analgesics was less in the alfentanil group ( P <0.05). We found, however, no major differences between the supplementations tested regarding the total dose of induction agent, emesis or time to discharge. Supplementation with 1.0 mg of alfentanil to propofol was found to be the best combination tested for short outpatient procedures.     

Antagonism of fentanyl and alfentanil by intravenous plus subcutaneous naloxone

Twenty patients undergoing microlaryngoscopy were anaesthetized with thiopentone. Half received fentanyl supplementation (about 8.5 micrograms/kg) and the other half alfentanil (about 65 micrograms/kg). Both groups were given naloxone 0.4 mg intravenously plus 0.4 mg subcutaneously shortly after the procedure which lasted some 12 minutes. The degree of ventilatory depression was assessed by a CO2 rebreathing test. The ventilation at an end-tidal PCO2 of 8.0 kPa (V8.0) was noted, and the findings related to a control value obtained on the day before anaesthesia. In the fentanyl group, V8.0 was significantly (p less than 0.05) less one hour after naloxone than 15 minutes after, and remained significantly below the control value for the first 8 hours after microlaryngoscopy. A second peak in plasma fentanyl concentration was observed four hours postoperatively in three patients. Respiratory depression in the alfentanil group was less pronounced and of shorter duration than in the fentanyl group. Postoperative plasma alfentanyl concentration decreased progressively with time in every patient.     

Comparison of effects of fentanyl and alfentanil on intra-ocular pressure

The effects of fentanyl and alfentanil on intra-ocular pressure during anaesthesia were investigated in 50 consecutive patients in a double-blind controlled trial. Both drugs produced a significant reduction in intraocular pressure (p less than 0.01). Alfentanil produced significantly greater reduction (48.5 percent) than fentanyl (28.6 percent) (p less than 0.01). A small but statistically significant reduction in arterial pressure (15 percent approximately) and heart rate (18 percent approximately), were observed with both agents, but no significant differences between them were noted. It is suggested that alfentanil may be a suitable alternative to fentanyl in ophthalmic anaesthesia.     

Effects of anaesthetic induction on myocardial function and metabolism: a comparison of fentanyl,sufentanil and alfentanil

Anaesthetic induction may induce myocardial ischaemia. A prospective randomized trial was instituted to compare the effect on ventricular function and myocardial metabolism of induction with fentanyl (FEN) or its analogues sufentanil (SUF) or alfentanil (ALF) in 96 patients undergoing elective coronary artery bypass grafting (CABG). Haemodynamic, metabolic (coronary sinus oxygen and lactate extraction) and gated ventrìculo graphic measurements were made awake pre-induction (PRE), after induction (IND) and after intubation (INT). Induction was performed with FEN 75 μg · kg^-1 SUF 15 μg · kg^-1 or ALF 125 μg · kg^-1 and metocurine. Fentanyl induction was associated with the greatest stability of mean arterial pressure (MAP), cardiac performance, and systolic function without associated myocardial lactate production. SUF produced the greatest depression of systolic function (p < 0.05) but without haemodynamic instability or myocardial lactate production in all but one patient. Induction with ALF produced the greatest reduction in MAP (p < 0.05) associated with the greatest decrease in diastolic compliance (p < 0.05) and 50 per cent incidence of myocardial lactate production (p < 0.05) with no significant change in coronary blood flow or myocardial oxygen consumption. ľinduction de ľanesthésie peut induire de ľischémie myocardique. Une étude prospective randomisée a été conduite afin de comparer ľeffet sur la fonction ventriculaire et le métabolisme myocardique de ľinduction avec le fentanyl (FEN) ou son analogue sufentanil (SUF) ou ľalfentanil(ALF) chez 96 patients devant subir une chirurgie de pontage aorto coronarien élective. Des mesures hémodynamiques, métaboliques (extraction de lactate ďoxyène du sinus coronaire) ainsi que des mesures de la fonction ventriculaire par des méthodes nucléaires étaient faites avant ľinduction (PRE), aprés ľinduction (IND) et après ľintubation (INT). ľinduction était faite avec du fentanyl 75 μg · kg^-1, sufentanil 15 μg · kg^-1 et fentanil 125 μg · kg^-1 associé à la métocurine. ľinduction avec le fentanyl a amené la plus grande stabilité de la pression artérielle moyenne (MAP), la performance cardiaque, et la fonction systolique sans production de lactate par le myocarde. Le sufentanil a produit la plus grande dépression de la fonction systolique (p < 0.05) sans instabilité hémodynamique ou production de lactate par le myocarde chez tous les patients sauf un. ľinduction avec ľalfentanil a produit la plus grande réduction de la pression artérielle moyenne (p < 0.05) associé avec la plus grande diminution de la compliance diastolique (p < 0.05) et 50 pour cent ďincidence de production de lactate par le mvocarde (p < 0.05) sans changement significatif dans le flot sanguin coronarien ou dans la consommation ďoxygène du myocarde.     

Effects of droperidol on peripheral vasculature: use of cardiopulmonary bypass as a study model

The effects of droperidol on the systemic vascular resistance (SVR) and the venous capacitance were studied during cardiopulmonary bypass (CPB) in 24 patients. CPB was performed with either pulsatile or non-pulsatile flow. During non-pulsatile flow, droperidol (0.15 mg X kg-1 and 0.30 mg X kg-1) decreased SVR and increased venous capacitance. These values were significantly different after the 2nd and the 7th min, respectively. During pulsatile flow, the initial SVR was lower. The decremental effect of 0.30 mg X kg-1 droperidol on SVR was proportional to the preinjection level of SVR (r = 0.64). The increase in venous capacitance related to droperidol was independent of the dose and of the type of flow in all patients. It can be concluded that the vasodilating action of droperidol during CPB on the arterial bed is transient, independent of dose, and related to the preinjection level of SVR. The effect of droperidol on venous capacitance is not as rapid but has a longer duration.     

Thiopentone reduces the haemodynamic response to induction of high–dose fentanyl–pancuronium anaesthesia in coronary artery surgical patients

Thirty-three coronary artery bypass graft patients anaesthetized with high-dose fentanyl (50 micrograms/kg)-pancuronium-oxygen were divided into one control group receiving additional saline and two groups receiving additional 1 mg/kg or 2.5 mg/kg of thiopentone before laryngoscopy and intubation. During laryngoscopy and intubation, systemic arterial pressures, heart rate and rate-pressure-product remained at considerably elevated levels caused by pancuronium in the control group. Both doses of thiopentone reduced these haemodynamic values close to their initial levels. Cardiac index and left ventricular stroke work index were significantly decreased, especially by the higher thiopentone dose, as compared with the control group. However, there were no statistical differences between the haemodynamic changes produced by the two doses of thiopentone. Sedative or hypnotic supplementation of high-dose fentanyl anaesthesia seems to be necessary if pancuronium is used as a muscle relaxant. A small increment of thiopentone, 1 mg/kg, was enough to return haemodynamic parameters almost to their initial levels, whereas the effect of 2.5 mg/kg of thiopentone was unnecessarily strong.     

A comparison of the effects of alfentanil/droperidol or fentanyl/droperidol on intra-ocular pressure

The influence of two intravenous sedative regimens on intra-ocular pressure was investigated in conjunction with retrobulbar local anaesthesia. Forty patients were allocated randomly to either group A (alfentanil and droperidol) or group F (fentanyl and droperidol). Measurements of intra-ocular pressure, arterial pressure and oxygen saturation were made before operation, after premedication, after intravenous sedation and after surgery. Paco2 was also measured before and after operation. Each sedation technique caused a similar reduction in intra-ocular pressure. There was less effect on Paco2 and oxygenation in group A.     

A cost-benefit evaluation of using propofol and alfentanil for a short gynecological procedure

It is well established that the immediate recovery after propofol or alfentanil anesthesia is short. Although the drugs themselves are more expensive than older drugs, a potential for saving costs arises. Concerning the benefits in terms of late recovery, less information is available. With vaginal termination of pregnancy (VTP), anesthesia is supposed to be the major cause of sick-leave. Does propofol and alfentanil anesthesia for VTP reduce sick-leave compared with thiopental and nitrous oxide anesthesia, and do the increased costs of the drugs outweigh the reduced costs of sick-leave? Data were obtained from 39 of 40 patients in ASA class I accepted for VTP and allocated to either propofol and alfentanil anesthesia (PA) or thiopental and nitrous oxide anesthesia (TN). A questionnaire was filled in by the patients at home after regaining full fitness. The number of patients with a sick-leave of 2 days or less in the groups was compared statistically with the number of patients with 3 days or more off work. The economic impact from the reported sick-leave was calculated for each study group, using data from national statistics. The figures were compared with the calculated costs of the drugs. The median number of days of sick-leave was 1 in the PA-group and 2 in the TN-group (range 0–3 and 0–5, respectively). Nineteen of the 20 patients in the PA-group and 13 of the 19 patients in the TN-group needed a short sick-leave period of 2 days or less (one-sided test of proportions, P<0.05). At the time of the study each patient was paid 210 SEK/day from the social insurance system and the mean cost of the drugs was 72 and 15 SEK/patient in the PA- and TN-groups, respectively. Using the mean difference in sick-leave between the groups of 0.8 days/patient (rather than the difference in median values of 1), a net gain of 111 SEK/patient was the result of changing from thiopental-nitrous oxide anesthesia to propofol-alfentanil anesthesia. Although the cost of drugs was higher, costs for the social insurance system and for the individuals themselves were reduced by almost 50%, when using the propofol and alfentanil combination, resulting in an overall benefit corresponding to almost twice the increase in the cost of anesthesia.     

Remifentanil, fentanyl, and alfentanil have no influence on the respiratory burst of human neutrophils in vitro

Background: Anaesthetic agents inhibit certain functions of human neutrophils. The respiratory burst (RB) enzyme in the plasma membrane of neutrophils leads to the production of superoxide anion. The oxygen radicals are responsible for killing phagocytised micro-organisms. We investigated the in vitro influence of remifentanil, fentanyl, and alfentanil on the respiratory burst of human neutrophils.
Methods: For the flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated with the tested drugs. The concentrations in vitro were adjusted to conform to the plasma concentrations reported for anaesthesia and also to 10-fold higher concentrations. The RB was measured by intracellular oxidation of dihydrorhodamine to fluorescent rhodamine after induction of phorbol-myristate-acetate (PMA), Escherichia coli (E. coli) or priming by tumour necrosis factor alpha followed by stimulation of n-formyl-methionyl-leucyl-phenylalanine (TNF-α/FMLP). In order to exclude prestimulation of the neutrophil granulocytes, negative controls were carried out. Propidium iodide (PI) was added for viability discrimination immediately prior to flow cytometry measurement.
Results: Regardless of the triggering agents chosen (PMA, E. coli , TNF-α/FMLP), remifentanil, fentanyl, and alfentanil had no significant effect on the neutrophils' respiratory burst even in concentrations which were higher than those encountered during in vivo conditions.
Conclusion: With respect to peri- and postoperative risk of infection, anaesthetics and analgetics with no inhibiting effect on neutrophil function should be used. These results show that remifentanil, fentanyl, and alfentanil do not influence the neutrophils' respiratory burst in vitro .     

Admixture of propofol and alfentanil

An admixture of propofol and alfentanil provides adequate sedation and analgesia during transvaginal oocyte retrieval in the absence of a paracervical block. In 100 patients the technique provided haemodynamic stability, sedation which was easily controlled, rapid recovery and universal patient acceptance.     

Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children

Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25..5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 μg/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration. The concentration of fentanyl in the venous reservoir, 2.06 to 11.64 ng/mL (7.04 ng/mL), was not significantly different from the plasma levels. The level of fentanyl in the filtrate was significantly less than the plasma levels, 0.243 to 1.87 ng/mL (0.894 ng/mL) at 5 minutes and 0.385 to 1.688 ng / mL (0.952 ng / mL) at 10 minutes into filtration; (P < 0.02 by the Wilcoxon signed-rank method). The data show that the plasma fentanyl concentration was not significantly reduced by modified ultrafiltration. The fentanyl levels found prefiltration were maintained postfiltration, and the observed changes in systemic arterial pressure were not due to an acute fall in the plasma concentration of analgesic drug.     

Intravenous anaesthesia with propofol and alfentanil. The influence of age and weight

Sixty healthy patients undergoing body surface surgery were anaesthetised with continuous infusions of propofol (200 micrograms/kg/minute) and alfentanil (0.25 microgram/kg/minute). Additional bolus doses of propofol (20 mg) were given if movement occurred. The incidence of patient movement in response to skin incision was significantly less in patients over 45 years of age than in those below 45 years (p less than 0.05). Maintenance dosage of propofol sufficient to abolish movement decreased with increasing age (p less than 0.001). Systolic blood pressure decreased in most patients over the first 10 minutes of anaesthesia and the magnitude of this decrease increased with age (p less than 0.0001). These parameters did not correlate strongly with body weight. Dose requirements of propofol are not the same for patients of all ages and strongly suggest that young and old patients should not be treated as a homogeneous group, either for investigative or clinical purposes.     

Anesthesia with alfentanil and methohexitone for short gynecological surgery

An anesthetic technique in which alfentanil hydrochloride, an ultra-short-acting opioid, was used as a substitute for N2O/O2 was evaluated in outpatient gynecological surgery. Methohexitone was used as a hypnotic agent. The following parameters were studied: blood pressure (BP) and heart rate before, during and at the end of surgery; the incidence of apnea longer than 20 s at induction; the awakening phase; immediate postoperative complications and later postoperative complications according to a questionnaire, including signs of thrombophlebitis. Eighty-nine patients were randomly allocated to three groups. Twenty-nine patients received alfentanil 7 micrograms/kg plus methohexitone plus O2/air (Group A7). Thirty patients received alfentanil 15 micrograms/kg plus methohexitone plus O2/air (Group A15). Thirty patients received thiopentone 5 mg/kg plus N2O/O2 (Group P, reference group). Neither in the A7-group, nor in the A15-group was there any increase in peroperative BP, while in the P-group both systolic and diastolic BP rose. The awakening phase was significantly shorter in both the A7- and A15-groups compared to the P-group. Apnea of clinical importance was only seen in the A15-group. There were few immediate postoperative complications in all groups, but the incidence of dizziness was significantly higher in the P-group. According to the questionnaire, the overall incidence of complaints the day after surgery was somewhat higher in the P-group. On the other hand, there was a somewhat higher incidence of thrombophlebitis in both A-groups. We may thus recommend the use of a combination of alfentanil 7 micrograms/kg plus methohexitone and air/oxygen for anesthesia in patients subjected to short gynecological procedures.     

Endogenous morphine is produced in response to cardiopulmonary bypass in neonatal pigs

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response. Endogenous morphine production has previously been demonstrated in humans after cardiac surgery with CPB. It has been hypothesized that morphine plays a role as an anti-inflammatory mediator in the systemic inflammatory response. The aim of this study was to investigate if the CPB procedure in itself elicits an endogenous morphine production in neonatal pigs. METHODS: Endogenous morphine production was measured in arterial blood in piglets exposed to sternotomy alone (sham group, n=10) or sternotomy and CPB (n=10). Blood samples were obtained immediately after the induction of anaesthesia, at the end of CPB and 4 h later. Morphine in arterial blood was detected by radioimmunoassay and confirmed by gas chromatography mass spectrometry. RESULTS: Animals undergoing CPB showed detectable endogenous morphine concentrations immediately after CPB, with increased concentrations postoperatively. There was no measurable morphine production in the sham operated pigs. CONCLUSION: The CPB procedures elicits an endogenous morphine production in neonatal pigs. This morphine response is analogous to the previously demonstrated response in patients subjected to cardiac surgery and CPB.