Pain on injection of propofol: The mitigating influence of metoclopramide using different techniques

Background: Metoclopramide administered intravenously (iv) immediately before injection of propofol, after mixing with propofol, or after a rubber tourniquet for 1 min before propofol injection will reduce pain induced by propofol injection. In this study, these three different techniques in reducing propofol injection pain with metoclopramide were compared with lidocaine or saline to evaluate the most effective method in reducing propofol injection pain.
Methods: In a randomized, semi-double-blind treatment, 175 patients were included into this study. Patients in group A were pretreated with metoclopramide 10 mg iv before propofol (2 mg/kg) induction. Patients in group B were induced with a mixture of propofol and metoclopramide. Patients in group C were pretreated with metoclopramide iv with a rubber tourniquet on the arm for 1 min followed by propofol administration. Groups D and E were identical to group C except for the replacement of pretreatment with either lidocaine (40 mg) or saline, respectively.
Results: Groups A, C and D (with active pain prophylaxis) showed a significantly less incidence of pain than the saline control group (E) as propofol was injected. There was no significance difference between metoclopramide and lidocaine in reducing propofol injection pain using a tourniquet technique. The intensity of the propofol injection pain (verbal pain score) was stronger with saline as compared with the other groups.
Conclusions: We conclude that iv retention of metoclopramide with tourniquet is as good as lidocaine and may be a useful alternative for reducing pain on propofol injection.     

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol

Background : Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent.
Method : In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 μg·kg^-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg·kg^-1doxapram or saline following infusion of propofol to loss of verbal contact.
Results : In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time.
Conclusion : We conclude that doxapram 0.5 mg·kg^-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.     

Influence of body compartments on propofol induction dose in female patients

Background: For induction of anaesthesia, drugs such as pro-pofol are commonly administered according to a per weight basis. However, drugs are primarily distributed to the fat-free mass. This study was undertaken to determine the relationship between propofol requirement for induction and body mass determined by bioimpedance analysis (BIA) or by body mass index (BMI).
Methods: Twenty-one ASA 1 female patients scheduled for gynaecologic surgery received propofol for induction at 133 mg. min^-1. Stepwise regression analysis was used to describe the relationships between propofol requirement for loss of consciousness and age, body weight, and lean body mass measured by BIA and BMI (independent variables).
Results: Loss of consciousness was obtained with a propofol dose (Mean (SEM)) of 2.170.10 mgkg^-1. Stepwise analysis showed that propofol requirement (total dose) was not proportional to weight or age but related to lean body mass as determined by BIA and to body mass index (r² = 0.447; global P - value <0.007). BMI was the only regressor variable when the propofol dose was expressed in mg. kg^-1 (r² = 0.661; P <0.001).
Conclusions: Our results indicate that propofol requirements for induction are proportional to the lean body mass rather than total body weight.     

Metoclopramide and prochlorperazine do not decrease propofol hypnotic requirements

One hundred patients scheduled for minor surgery were given either saline, metoclopramide 0.1 mg.kg^-1 or 0.2 mg.kg^-1, or prochlorperazine 0.1 mg.kg^-1 or 0.2 mg.kg^-1 before induction of anaesthesia with a fixed rate infusion of propofol. Neither metoclopramide nor prochlorperazine reduced the induction dose of propofol. The possibility that these agents increased the induction dose could not be excluded.     

The influence of age and administration rate on the brain sensitivity to propofol in rats

Background: It is well established that the dose of propofol for induction of anaesthesia is influenced by patient age. This may be explained by differences in pharmacokinetics or pharmaco-dynamics. To evaluate the effect of age on propofol pharmaco-dynamics, the brain concentration of propofol at the time of an EEG end-point was used as a measure of CNS sensitivity.
Methods: Ninety-five rats were assigned to 4 groups. Anaesthesia was induced by continuous propofol infusion at different rates. The dose of propofol and duration of anaesthesia were determined from 23 up to 776 days of age. The rats were killed at 23,287 or 776 days of age at the EEG end-point and samples of cerebral cortex, midbrain, cerebellum, serum and fat tissue were submitted to HPLC analysis of propofol concentrations.
Results: The induction dose of propofol varied with age and administration rate. Young animals needed a higher dose of propofol. Old animals had higher brain concentrations of propofol at the EEG end-point than young animals. However, propofol concentrations in serum were higher in young animals. The propofol concentration in the brain was influenced by the administration rate.
Conclusion: The dose of propofol for induction of anaesthesia in rats is influenced by animal age and administration rate. Young animals need a larger induction dose than old rats, but are more sensitive as measured by the brain concentration of propofol. The larger induction dose in young rats when compared with adults is explained by pharmacokinetic differences rather than by pharmacodynamic changes.     

The effect of topical lignocaine on intubating conditions after propofol-alfentanil induction

Background: Recent studies have found satisfactory conditions for intubation of the trachea without using muscle relaxants using an intravenous technique combining propofol and alfentanil. In this study we evaluate intubating conditions with this method and either lignocaine applied topically in the larynx and trachea or placebo.
Methods: Sixty adult patients of ASA class I were premedicated with diazepam 15–20 mg and randomly allocated to one of two groups. For induction of anaesthesia both groups were given propofol 2.5 mg/kg and alfentanil 30 μg/kg. One group received 4 ml of lignocaine 40 mg/ml (≤3 mg/kg) topically into the larynx and trachea (group L), the other group an equal amount of isotonic saline (group S) in a double-blind design. Intubation conditions were assessed as excellent, good, moderately good, poor or impossible, scored on the basis of jaw relaxation, ease of insertion of the tube and coughing on intubation.
Results: The total score for group L was significantly better than the score for group S ( P <0.0001) with significant differences with respect to ease of intubation and coughing after intubation.
Conclusions: Induction of anaesthesia with propofol 2.5 mg/kg and alfentanil 30 μg/kg combined with 4 ml of lignocaine-spray 40 mg/ml into the larynx and trachea offered consistent and satisfactory intubation conditions. We thus recommend this method for tracheal intubation, where the use of muscle relaxants is not indicated.     

Propofol-thiopentone admixture-hypnotic dose, pain on injection and effect on blood pressure.

This study examined some pharmacodynamic characteristics of two admixtures of propofol and thiopentone. Ninety unpremedicated ASA 1 or 2 patients were group-randomized to receive, in a double-blinded manner, one of the following mixtures for induction of anaesthesia: Group P50: propofol 1% 10 ml/thiopentone 2.5% 10 ml; Group P75: propofol 1% 15 ml/thiopentone 2.5% 5 ml; Group P100: propofol 1% 20 ml/lignocaine 1% 4 ml. An additional 30 randomized but unblinded patients from the same patient cohort received thiopentone 2.5% to provide predictive dose data for groups P50 and P75. Haemodynamic data were collected pre- and post-induction. The required induction dose of both mixtures of propofol and thiopentone found an additive rather than a synergistic interaction with no significant difference between predicted and observed dose. Thiopentone resulted in significantly more rapid induction of anaesthesia than propofol/lignocaine or propofol/thiopentone. The addition of thiopentone to propofol was found to be as efficacious as the mixing of lignocaine with propofol in reducing pain on injection. The fall in systolic blood pressure was significantly less in group P50 compared with groups P75 or P100. Admixture of thiopentone with propofol results in an additive hypnotic effect, a reduction in pain of injection (comparable with addition of lignocaine) and a reduced hypotensive response compared to propofol injection alone during induction.     

Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide during and after spinal anaesthesia for caesarean section: A randomized, double-blind, placebo-controlled trial

Background: Nausea and vomiting during and after spinal anaesthesia for caesarean section are distressing to the patient. This study was undertaken to evaluate the efficacy and safety of granisetron, droperidol and metoclopramide for the prevention of nausea and vomiting in parturients undergoing caesarean section under spinal anaesthesia.
Methods: In a randomized, double-blind, placebo-controlled trial, 120 patients received granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg or placebo (saline) ( n =30 of each) i. v. immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during and after spinal anaesthesia for caesarean section.
Results: The incidence of intraoperative, post-delivery nausea and vomiting was 13%, 17%, 20% and 63% after administration of granisetron, droperidol, metoclopramide and placebo, respectively; the corresponding incidence during 0–3 h after surgery was 7%, 27%, 27% and 43%; the corresponding incidence during 3–24 h after surgery was 7%, 20%, 23% and 37% ( P <0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups.
Conclusion: Granisetron is highly effective for preventing nausea and vomiting during and after spinal anaesthesia for caesarean section. Droperidol and metoclopramide are effective for the prevention of intraoperative, post-delivery emesis, but are ineffective for the reduction of the incidence of postoperative emesis.     

Regular tramadol use does not affect the propofol dose requirement for induction of anaesthesia

BACKGROUND AND OBJECTIVES: An increased risk of awareness during general anaesthesia in patients receiving tramadol has been reported. We studied whether tramadol affects the amount of propofol required for induction of anaesthesia. METHODS: In this prospective controlled study, we evaluated 46 patients, half of whom used tramadol regularly. Entropy indices, state entropy and response entropy, were used to assess the level of hypnosis. Patients were anaesthetized with a propofol infusion (1 mg kg(-1) min(-1)) until they first became unconscious, and further until they developed a burst suppression pattern in the electroencephalogram. The doses of propofol needed to reach these end-points were recorded. RESULTS: The amount (median, (range)) of propofol required for loss of consciousness was 2.0 (1.0-5.5) mg kg(-1) and 2.4 (0.9-8.3) mg kg(-1) (P=0.95) in the tramadol users and controls, respectively. The amount of propofol required for burst suppression was 5.8 (3.9-12.7) mg kg(-1) and 6.4 (2.9-15.1) mg kg(-1) (P=0.89) in the tramadol users and controls. There was no difference between the groups in state entropy and response entropy during different stages of induction of anaesthesia. CONCLUSIONS: Tramadol did not affect the dose of propofol required to achieve loss of consciousness or burst suppression pattern in electroencephalogram during induction of general anaesthesia. However, there was a ninefold inter-individual variation in propofol dose requirement for loss of consciousness and a fivefold variation for reaching burst suppression. Due to extensive inter-individual variability, monitoring the level of hypnosis during general anaesthesia using propofol may enhance the correct dosage.     

A comparison between midazolam co-induction and propofol predosing for the induction of anaesthesia in the elderly

In a prospective, double-blind, randomised, placebo-controlled trial, we have compared the effects of midazolam co-induction with propofol predosing on the induction dose requirements of propofol in elderly patients. We enrolled 60 patients aged > 70 years, attending for urological surgery. The patients were allocated randomly to one of three groups, to receive either midazolam 0.02 mg.kg(-1), propofol 0.25 mg.kg(-1), or normal saline 2 ml (placebo) 2 min prior to induction of anaesthesia using propofol 1% infusion at 300 ml.h(-1). The propofol dose requirements for induction were recorded for two end-points (loss of verbal contact and insertion of an oropharyngeal airway). Cardiovascular parameters were recorded at 1-min intervals for each patient until induction was complete. The midazolam group showed a significant reduction in propofol dose requirements for induction (p = 0.05) compared to the placebo group. The propofol group did not show a significant dose reduction compared to placebo. There were no demonstrable differences in terms of improved cardiovascular stability between groups. We conclude that propofol predosing does not significantly reduce the induction dose of propofol required in the elderly, and there were no cardiovascular benefits to either midazolam co-induction or propofol predosing in the elderly.     

Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery

We propose the use of an intravenous propofol/propofol auto-co-induction technique as an alternative to propofol/midazolam for induction of anaesthesia. We have studied 54 unpremedicated ASA 1 or 2 patients undergoing day-stay anaesthesia for minor orthopaedic surgery. All received 10 micrograms.kg-1 or alfentanil before induction, followed by either midazolam 0.05 mg.kg-1, propofol 0.4 mg.kg-1 or saline, and 2 min later, a propofol infusion at a rate of 50 mg.kg-1.h-1 until loss of eyelash reflex. We compared pre- and postinduction haemodynamic changes, complications at insertion of a laryngeal mask airway and recovery from anaesthesia in the three groups. Both co-induction techniques showed less postinduction hypotension and significant reduction of the total induction dose of propofol when compared to the control group. In the propofol/propofol group there was a decreased incidence of apnoea during induction of anaesthesia. These patients were discharged from hospital 2 h after the end of anaesthesia whereas patients in the midazolam/propofol group were discharged after 2 1/2 h (p < 0.001).     

Metoclopramide does not influence the frequency of propofol-induced spontaneous movements

STUDY OBJECTIVE: To evaluate the effects of metoclopramide on the frequency and severity of propofol-induced movements. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: Veterans Administration Medical Center. PATIENTS: One hundred thirty-seven consenting adults scheduled to receive general anesthesia with propofol induction. INTERVENTIONS: Patients were randomized to receive either metoclopramide 10 mg intravenously (IV) or placebo (saline) 3 min before induction of general anesthesia. All patients received midazolam 1 to 2 mg IV, fentanyl 50 to 150 microg IV, and lidocaine 50 to 80 mg IV before induction of anesthesia. MEASUREMENTS: Occurrence of spontaneous movements and severity during the observation period were recorded after propofol induction by observing movement in the hands/arms and feet/legs, as well as presence of a hiccup. The dosage of anesthetic medications administered was also recorded for each patient. MAIN RESULTS: No differences were noted in the frequency and severity of spontaneous movement in the patients who had received metoclopramide and placebo. However, compared with the patients who did not move, patients who experienced movements received a significantly higher dose of propofol (P = 0.025) and a lower dose of fentanyl (P = 0.049). CONCLUSIONS: Metoclopramide does not affect the frequency of propofol-induced movements, but propofol and fentanyl doses influence the frequency of movements during propofol induction.     

Prevention of nausea and vomiting in female patients undergoing breast surgery: A comparison with granisetron, droperidol, metoclopramide and placebo

Background : Breast surgery is associated with a relatively high incidence of postoperative nausea and vomiting (PONV). This study was undertaken to evaluate the efficacy of granisetron, droperidol and metoclopramide for preventing PONV after breast surgery.
Methods : In a randomized, double-blind, placebo-controlled trial, 120 female patients received granisetron 40μg.kg^-1, droperidol 1.25 mg, metoclopramide 10 mg or placebo (saline) (n=30 for each) intravenously immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. Postoperatively, during the first 24 h after anaesthesia, the incidence of PONV and adverse events was recorded.
Results : The incidence of PONV was 17% with granisetron, 37% with droperidol, 43% with metoclopramide and 50% with placebo ( P <0.05; overall Fisher's exact probability test). The incidence of adverse events was not different among the groups.
Conclusion : Granisetron is highly effective for reducing the incidence of PONV in female patients undergoing breast surgery. Droperidol and metoclopramide are ineffective in this population.     

A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia

In a double-blind, placebo-controlled study of 90 ASA 1 and 2 patients scheduled for elective surgery we compared the effect of pre-administering midazolam 2 mg or propofol 30 mg on the dose of propofol subsequently required to induce anaesthesia. Using loss of response to verbal command and tolerance to placement of a facemask as end-points, the dose of propofol required to induce anaesthesia was significantly smaller in the patients given propofol (1.87 mg.kg-1) or midazolam (1.71 mg.kg-1) when compared to the control group (2.38 mg.kg-1). Although the decrease in blood pressure following induction was no difference between the two study groups and the decrease was felt not to be of clinical significance in this group of patients. As propofol is presented ' ... for use in a single patient only' and the technique of predosing with propofol allowed induction of all patients with less than 200 mg (a single ampoule), we question on a cost basis whether midazolam co-induction is necessary to reduce propofol induction doses.     

Posttonsillectomy vomiting. Ondansetron or metoclopramide during paediatric tonsillectomy: are two doses better than one?

This randomized, double blinded, placebo controlled, prospective study compared the antiemetic efficacy of one preoperative dose of metoclopramide 0.25 mg·kg^?1 intravenously or ondansetron 0.15 mg·kg^?1 intravenously with two doses of the same drugs (second dose administered one h postoperatively) in 200 preadolescent children undergoing tonsillectomy with either isoflurane or propofol anaesthesia. The incidence of posttonsillectomy vomiting was significantly reduced (P < 0.005) by two doses of either metoclopramide or ondansetron (18% and 8%, respectively) compared with placebo (50%). No difference in posttonsillectomy vomiting exists between the children who received isoflurane and those who received a propofol infusion. Our results suggest that two doses of metoclopramide 0.25 mg·kg^?1 intravenously, like two doses of ondansetron 0.15 mg·kg^?1, are effective in reducing vomiting after tonsillectomy in children who have received either isoflurane or propofol anaesthesia.     

Haemodynamic effects of propofol in children

The haemodynamic effects of induction of anaesthesia with propofol in children were studied. Two hundred and sixteen children (ASA 1) were randomly allocated to receive one of six different doses of propofol, from 1.6 mg/kg to 2.6 mg/kg, in 0.2 mg/kg increments. Noninvasive measurement of blood pressure showed that mean arterial pressure was reduced by approximately 15% after 1 minute, and by 30% after 5 minutes. The reduction in pulse rate over a 5-minute period was approximately 17%. These changes were similar in each group, regardless of the dose administered. The propofol was mixed with lignocaine, 0.5 mg/ml, and the incidence of pain on injection into a vein on the dorsum of the hand was 24%. We conclude that, within the dose range of our study, the haemodynamic disturbance after induction of anaesthesia with propofol in children is not dose related.     

Optimum bolus dose of propofol for tracheal intubation during sevoflurane induction without neuromuscular blockade in children

The purpose of this study was to determine the optimum bolus dose of propofol required to provide excellent conditions for tracheal intubation following inhalational induction of anaesthesia using 5% sevoflurane without neuromuscular blockade. Twenty-eight children, aged three to seven years, requiring anaesthesia for short duration surgery were recruited. Two minutes after beginning the inhalational induction with 5% sevoflurane and 60% nitrous oxide, a predetermined dose of propofol was injected over 10 seconds. Propofol dose was determined using the Dixon's up-and-down method, starting from 3 mg/kg (0.5 mg/kg as a step size). Laryngoscopy was performed 50 seconds after propofol injection. The optimum dose of propofol required for excellent intubating conditions was 1.39 +/- 0.37 mg/kg in 50% of children during inhalation induction using 5% sevoflurane and 60% nitrous oxide in the absence of neuromuscular blocking agents. From probit analysis, the 95% effective dose of propofol was 2.33 mg/kg (95% confidence interval 1.78 to 6.21 mg/kg).     

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.     

Comparison of subhypnotic doses of thiopentone vs propofol on the incidence of postoperative nausea and vomiting following middle ear surgery

Background : Middle ear surgery is associated with a high incidence of emetic sequelae and propofol has been reported to have antiemetic activity in subhypnotic doses.
Methods : In a double-blind, randomized study, the patients received either thiopentone 1.0 mg.kg^-1 (n=26) or 0.5 mg.kg^-1 propofol (n=26) at the end of middle ear surgery under isoflurane-N₂O-fentanyl-vecuronium anaesthesia. Trained nurses, unaware of the group assignment, assessed postoperative nausea, retching and vomiting up to 24 h after the end of anaesthesia. Droperidol 10μg.kg^-1 was used as a "rescue" antiemetic.
Results : The main result was that the patients in the propofol group did not suffer from retching and vomiting (R&V) during the first 6 h, whereas these symptoms occurred in 46% ( P <0.001) of the patients in the thiopentone group. The patients in the propofol group needed significantly less droperidol during the first 24 h (mean number of doses 0.39 ± 0.57 (SD)) than the patients in the thiopentone group (1.35 ± 1.47, P <0.005). Treatment with propofol was a predictor for lowered incidence of R&V, as well as male gender and negative history of motion sickness.
Conclusion : Propofol at a subhypnotic dose of 0.5 mg.kg^-1 provides prophylaxis against retching and vomiting for the first 6 h postoperatively after middle ear surgery. The incidence of nausea was not reduced by propofol.     

Effect of metoclopramide on pain on injection of propofol

We undertook a randomized, double-blind, placebo-controlled study to examine the efficacy of metoclopramide at three different doses (2.5 mg, 5 mg, 10 mg) for reducing pain on injection of propofol in 100 patients scheduled for elective surgery. Patients received intravenously the study drug, with venous occlusion for one minute, followed by propofol 2 mg/kg into a dorsal hand vein. The incidence of pain was significantly less in patients receiving metoclopramide 5 mg (32%) or 10 mg (28%) than in patients receiving placebo (80%) (P<0.01). No difference between metoclopramide 2.5 mg and the placebo groups was found. We conclude that pretreatment of a dorsal hand vein with metoclopramide in a dose of 5 or 10 mg, with venous occlusion for one minute, effectively decreases the incidence of pain caused by propofol injection.