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K T Olkkola

Publications and source records attributed to K T Olkkola.

At least 19 recordsLinked to original sources
PubMed2006

Isobaric bupivacaine via spinal catheter for hip replacement surgery: ED50 and ED95 dose determination.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of the local anaesthetic and, consequently, less haemodynamic change. However, little is known about the required doses. Therefore, we designed a study to assess the local anaesthetic doses of isobaric bupivacaine which were effective in 50% (ED50) and 95% (ED95) of patients undergoing hip replacement surgery. METHODS: Forty-eight patients undergoing hip replacement surgery were randomly allocated to one of six possible groups of eight patients to receive 6, 7, 8, 9, 10 or 12 mg of isobaric bupivacaine in a double-blind manner. The ED50 and ED95 values were calculated by a logistic regression model. The position of the spinal catheter tip was confirmed by X-rays. RESULTS: The ED50 and ED95 values were 7.1 mg (95% confidence interval, 6.0-8.4) and 12.3 mg (95% confidence interval, 8.9-15.7), respectively. The location of the tip of the intrathecal catheter had no effect on local anaesthetic requirements. Eight patients required ephedrine after anaesthesia induction and a further 11 patients required ephedrine for correction of hypotension during surgery. CONCLUSION: The observed ED50 and ED95 values may guide us to use small doses of isobaric bupivacaine for hip replacement surgery. Hypotension is still possible even if low doses of isobaric bupivacaine are used.

Adult↗
PubMed2005

Effect of ciprofloxin on the pharmacokinetics of intravenous lidocaine.

BACKGROUND AND OBJECTIVE: Recent studies have suggested that cytochrome P-450 isoenzyme 1A2 has an important role in lidocaine biotransformation. We have studied the effect of a cytochrome P-450 1A2 inhibitor, ciprofloxacin, on the pharmacokinetics of lidocaine. METHODS: In a randomized, double-blinded, cross-over study, nine healthy volunteers ingested for 2.5 days 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 1.5 mg kg[-1] lidocaine intravenously over 60 min. Plasma concentrations of lidocaine, 3-hydroxylidocaine and monoethylglycinexylidide were determined for 11 h after the start of the lidocaine infusion. RESULTS: Ciprofloxacin increased the mean peak concentration and area under plasma concentration-time curve of lidocaine by 12% (range [-6] to+46%; P<0.05) and 26% (8--59%; P 0.01), respectively. The mean plasma clearance of lidocaine was decreased by ciprofloxacin by 22% (7--38%; P<0.01). Ciprofloxacin decreased the area under the plasma concentration-time curve of monoethylglycinexylidide by 21% (P<0.01) and that of 3-hydroxylidocaine by 14% (P< 0.01). CONCLUSION: The plasma decay of intravenously administered lidocaine is modestly delayed by concomitantly administered ciprofloxacin. Ciprofloxacin may increase the systemic toxicity of lidocaine.

Adult↗
PubMed2004

Minimum effective local anaesthetic dose of isobaric levobupivacaine and ropivacaine administered via a spinal catheter for hip replacement surgery.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of local anaesthetic and, consequently, less haemodynamic changes. However, little is known about the required doses. Therefore, we designed a study to assess the minimum effective local anaesthetic dose (MLAD) of levobupivacaine and ropivacaine in this context. METHODS: Forty-one patients undergoing hip replacement surgery were randomly allocated to one of the two local anaesthetic groups in a double-blind manner. The initial dose of local anaesthetic was determined by the response of the previous patient: the effective dose resulted in a 1 mg decrease in the dose of levobupivacaine or ropivacaine, and an ineffective dose resulted in a 1 mg increase. The MLAD was calculated by the Dixon up-and-down method. RESULTS: The MLAD of levobupivacaine was 11.7 mg (95% CI, 11.1-12.4) and that of ropivacaine 12.8 mg (95% CI, 12.2-13.4). CONCLUSIONS: These doses are significantly smaller than doses reported before for single-shot spinal anaesthesia. Continuous spinal anaesthesia allows the use of relatively small doses of local anaesthetic.

Adult↗
PubMed2002

Impact of age, submersion time and water temperature on outcome in near-drowning.

BACKGROUND: Because children have less subcutaneous fat, and a higher surface area to body weight ratio than adults, it has been suggested that children cool more rapidly during submersion, and therefore have a better outcome following near-drowning incidents. AIM OF THE STUDY: To study the impact of age, submersion time, water temperature and rectal temperature in the emergency room on outcome in near-drowning. MATERIAL AND METHODS: This retrospective study included all near-drowning victims admitted to the intensive care units of Helsinki University Central Hospital after successful cardiopulmonary resuscitation between 1985 and 1997. RESULTS: There were 61 near-drowning victims (age range: 0.5-60 years, median 29 years). Males were in the majority (40), and 26 were children (<16 years). The median water temperature was 17 degrees C (range: 0-33 degrees C). The median submersion time for the 43 survivors (70%) was 10 min (range: 1-38 min). Intact survivors and those with mild neurological disability (n=26, 43%) had a median submersion time of 5 min (range: 1-21 min). In non-survivors the median submersion time was 16 min (range: 2-75 min). Submersion time was the only independent predictor of survival in linear regression analysis (P<0.01). Patient age, water temperature and rectal temperature in the emergency room were not significant predictors of survival. CONCLUSIONS: Although submersion time is usually an estimate, it is the best prognostic factor after a near drowning incident. Children did not have a better outcome than adults.

Adolescent↗
PubMed2001

Perioperative determinants and outcome of cardiopulmonary arrest in children after heart surgery.

OBJECTIVES: To identify perioperative factors associated with postoperative cardiopulmonary arrest (CA) in the pediatric intensive care unit (PICU) in children undergoing cardiovascular surgery, and to report the outcome of cardiopulmonary resuscitation (CPR) in these patients. METHODS: We reviewed the medical records of all patients under 16 years of age who had undergone cardiovascular surgery and sustained CA in PICU in an urban, tertiary care children's hospital over a 5-year period. We used two control groups of patients who recovered without CA. (1) Sixty-five patients, who were operated under deep hypothermic circulatory arrest (DHCA) during the study period. (2) All patients who underwent repair of congenital heart lesions without DHCA in 1994 (n=278). RESULTS: Eighty-two children experienced CA during postoperative care in PICU, mainly from cardiovascular causes. Thirty-four (41%) were declared dead without attempted resuscitation, CPR was initiated in 48 (59%). The primary survival rate was 56% and 1 year survival rate was 19%. The incidence of CA was 3.6% for closed heart operations, 4.9% for intra-cardiac surgery without DHCA, and 27% for operations involving DHCA. Thirty-three per cent of patients with CA arrested during the first 24 postoperative h. Preoperative mechanical ventilation (P=0.03), prostaglandin E1 (P=0.001) and inotropic support (P=0.04) were given significantly more frequently to patients who postoperatively required CPR, compared to control groups. Patients in whom CPR was attempted were younger than the 1994 controls (0.4 vs. 1.2 years; P<0.04), had longer mean aortic-cross-clamp times (76 vs. 51 min; P<0.0001) and cardiopulmonary bypass times (124 vs. 85 min; P<0.0002), and required more inotropic support upon leaving the operating room (P<0.0001). Patients who received CPR had significantly longer DHCA times (53 vs. 32 min; P<0.0002) and required more inotropic support than patients in the DHCA control group (P<0.002). CONCLUSIONS: CA after pediatric cardiac surgery is associated with repair of complex congenital heart anomalies in patients who require preoperative mechanical ventilation and vasoactive agents, prolonged aortic cross-clamp, circulatory arrest; and heavy postoperative inotropic support.

Cardiac Surgical Procedures↗
PubMed2001

Effect of clarithromycin and itraconazole on the pharmacokinetics of ropivacaine.

In a double-blind, randomised, three-way cross-over study, eight healthy volunteers ingested daily for 4 days either 250 mg clarithromycin twice daily, 200 mg itraconazole once daily, or placebo. On day 4, each subject received a single dose of 0.6 mg kg-1 ropivacaine intravenously over 30 min. Ropivacaine and (S)-2',6'-pipecoloxylidide in venous plasma and urine samples were measured for up to 12 hours and 24 hours, respectively. There were no significant changes in the pharmacokinetic parameters of the parent ropivacaine after ingestion of clarithromycin or itraconazole. However, the peak plasma concentration and AUC of (S)-2',6'-pipecoloxylidide metabolite were significantly decreased in both the clarithromycin and itraconazole phases, compared with the placebo phase. The fraction of ropivacaine metabolised to (S)-2',6'-pipecoloxylidide excreted in urine was decreased in the itraconazole phase. Both clarithromycin and itraconazole inhibit the CYP3A4 mediated formation of (S)-2',6'-pipecoloxylidide from ropivacaine. With the doses used, itraconazole is a stronger inhibitor than clarithromycin. The interaction of clarithromycin with ropivacaine seems to be dose (concentration)-dependent.

Administration, Oral↗
PubMed2001

Drug interactions.

The prevalence of undesirable drug interactions is substantial but largely unknown. Although drug interactions are certainly an important cause of drug toxicity, their clinical significance may have been exaggerated. This review presents a brief overview of possible drug interactions.

Journal Article↗
PubMed2001

Effect of rifampin and tobacco smoking on the pharmacokinetics of ropivacaine.

OBJECTIVE: Our objective was to assess the effect of rifampin (INN, rifampicin) and tobacco smoking on the pharmacokinetics of ropivacaine. METHODS: A randomized, 2-phase, crossover study was performed in both a group of 10 healthy nonsmokers and a group of 8 healthy smokers. In both groups each subject ingested daily for 5 days either placebo or 600 mg rifampin. On day 6 each subject received intravenously over 30 minutes a single dose of 0.6 mg/kg ropivacaine. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S) -2',6'-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 hours and 24 hours, respectively. Pharmacokinetic parameters were calculated with noncompartmental methods, and t tests were used for comparisons between the phases and between the smokers and nonsmokers. The electrocardiogram was monitored for 3 hours. RESULTS: There were no statistically significant differences in the area under the plasma concentration-time curve (AUC), plasma clearance (CL), or half-life (t(1/2)) of ropivacaine between the smokers and nonsmokers. However, smokers excreted in urine 31% more 3-OH-ropivacaine and 62% less PPX than nonsmokers did. Rifampin decreased the AUC of ropivacaine in nonsmokers by 52% and in smokers by 38%. In nonsmokers rifampin increased the CL of ropivacaine by 93% and shortened its t(1/2) by 25%. In smokers rifampin increased the CL of ropivacaine by 47% and shortened its t(1/2) by 20%. Rifampin decreased the urinary excretion of 3-OH-ropivacaine in nonsmokers by 74% and in smokers by 68%, and it increased the excretion of PPX by 97% and 158%, respectively. No clinically significant differences in the QTc times were found between the groups or treatments. CONCLUSIONS: Tobacco smoking increases the excretion of 3-OH-ropivacaine in urine, probably because of the increased cytochrome P450 (CYP) 1A2-mediated metabolism of ropivacaine, and decreases the excretion of CYP3A4-formed PPX in urine. Rifampin considerably increases the metabolism of ropivacaine to PPX and decreases the metabolism to 3-OH-ropivacaine in both nonsmokers and smokers.

Adult↗
PubMed2000

Utstein style reporting of in-hospital paediatric cardiopulmonary resuscitation.

STUDY OBJECTIVE: To report paediatric in-hospital cardiac arrest data according to Utstein style and to determine the effectiveness of cardiopulmonary resuscitation (CPR) in hospitalized children. DESIGN: Retrospective 5-year case series. SETTING: Urban, tertiary-care children's hospital. PARTICIPANTS: All patients who sustained cardiopulmonary arrest. RESULTS: Altogether 227 patients experienced a cardiopulmonary arrest during the study period, 109 (48.0%) were declared dead without attempted resuscitation, and CPR was initiated in 118 (52.0%). The incidence of cardiac arrest was 0. 7% of all hospital admissions and 5.5% of PICU admissions; the incidence of CPR attempts was 0.4 and 2.5%, respectively. Most of the CPR attempts (64.4%) took place in the PICU and the most frequent aetiology was cardiovascular (71.2%). The 1-year survival rate was 17.8%. Short duration of external CPR was the best prognostic factor associated with survival. With few exceptions, the Paediatric Utstein Style was found to be applicable for reporting retrospective data from in-hospital cardiac arrests in children. CONCLUSIONS: In-hospital cardiopulmonary resuscitation was shown to be an uncommon event in children; the survival rate was similar to earlier studies.

Adolescent↗
PubMed2000

Pharmacokinetics of amrinone in neonates and infants.

OBJECTIVE: To evaluate the pharmacokinetics of amrinone and its metabolites in neonates and infants after reconstructive surgery for congenital heart disease. DESIGN: Prospective study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Fifteen neonates aged less than 1 month with transposition of the great arteries and 14 infants aged 2 to 6 months with complete atrioventricular septal defect. INTERVENTIONS: Amrinone, loading dose of 2 mg/kg, was administered before weaning from cardiopulmonary bypass, followed by a maintenance infusion of 7.5 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: Blood samples to determine plasma concentrations of amrinone, N-acetylamrinone, and N-glycolylamrinone were drawn before amrinone administration, frequently after the loading dose, every 6 hours during the maintenance infusion, and until 48 hours after the end of the infusion. Amrinone clearance was 2.4 +/- 0.9 mL/kg/min in neonates and 3.2 +/- 1.2 mL/kg/min in infants (p < 0.05). The volume of distribution at steady-state was smaller (p < 0.05) in neonates than in infants. The elimination half-life of amrinone was 10.7 +/- 6.7 hours in neonates and 6.1 +/- 1.4 hours in infants (p < 0.05). There was a linear correlation between the clearance of amrinone and the body surface area (r = 0.67; p < 0.05). The ratio of the plasma concentration of N-acetylamrinone to that of amrinone did not differ between neonates and infants. CONCLUSIONS: Amrinone is eliminated at a slower rate in neonates than in infants. The rate of acetylation of amrinone appears to be similar; the differences in the elimination capacity of amrinone are mainly due to the immature renal function in neonates.

Amrinone↗
PubMed2000

Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery.

We have studied the pharmacokinetics and pharmacodynamics of alfentanil, fentanyl and sufentanil together with propofol in patients undergoing coronary artery bypass graft surgery (CABG). Sixty patients (age 40-73 yr, 56 male) were assigned randomly to receive alfentanil, fentanyl or sufentanil and propofol. Plasma concentrations of these drugs and times for the plasma concentration to decrease by 50% (t50) and 80% (t80) after cessation of the infusion were determined. Times were recorded to awakening and tracheal extubation. Total dose and plasma concentrations of propofol were similar in all groups. Mean total doses of alfentanil, fentanyl and sufentanil were 443, 45 and 4.4 micrograms kg-1, respectively. Time to awakening did not differ significantly. In patients receiving fentanyl, the trachea was extubated on average 2 h later than in those receiving sufentanil and 3 h later than in those receiving alfentanil (P < 0.05). The t80 of fentanyl was longer (P < 0.05) than that of alfentanil or sufentanil, and there was a linear correlation between the t80 of the opioid and the time to tracheal extubation (r = 0.51; P < 0.01). However, the t50 values for these opioids were similar and did not correlate with recovery time. In conclusion, patients undergoing CABG and who were anaesthetized with fentanyl and propofol needed mechanical ventilatory support for a significantly longer time than those receiving alfentanil or sufentanil and propofol. On the basis of the interindividual variation observed, the time to tracheal extubation was most predictable in patients receiving alfentanil and most variable in patients receiving fentanyl, a finding which may be important if the patients are transferred to a step-down unit on the evening of the operation.

Adult↗
PubMed2000

Rapacuronium 2.0 or 2.5 mg kg-1 for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg-1.

The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg-1 is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg-1 during rapid-sequence induction of anaesthesia with fentanyl 1-2 micrograms kg-1 and thiopental 2-7 mg kg-1. Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg-1 respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg-1 was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg-1 it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg-1. The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P < 0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg-1 respectively (P < 0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg-1 could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction.

Adolescent↗
PubMed2000

A comparison of remifentanil and alfentanil for use with propofol in patients undergoing minimally invasive coronary artery bypass surgery.

UNLABELLED: Most patients undergoing minimally invasive direct coronary artery bypass surgery can be awakened and tracheally extubated in the operating room. We have compared two techniques of total IV anesthesia in this patient population: 30 patients (aged 44 to 74 yr; 24 male) premedicated with temazepam were randomly assigned to receive either remifentanil-propofol or alfentanil-propofol. Anesthesia was induced with remifentanil 2 microg/kg or with alfentanil 40 microg/kg, with propofol, and maintained with remifentanil at 0.25 or 0.5 microg x kg(-1) x min(-1) or alfentanil at 0.5 or 1 microg x kg(-1) x min(-1). The stable maintenance infusion rate of propofol was adjusted for age. Times to awakening and tracheal extubation were recorded. Postoperatively, IV morphine provided by patient-controlled analgesia was used for 48 h. Times to awakening and tracheal extubation (mean +/- SD) were shorter (P < 0. 01) in patients receiving remifentanil, and interpatient variations in times to awakening and tracheal extubation smaller (awakening 25 +/- 7 vs 74 +/- 32 min, and extubation 27 +/- 7 vs 77 +/- 32 min). Analysis of variance revealed that postoperative consumption of morphine was dependent on both the intraoperative opioid and the time elapsed after surgery (P < 0.05): patient-controlled analgesia morphine use during the first 3 h after awakening was more in patients receiving remifentanil (P < 0.01). IMPLICATIONS: Recovery of patients undergoing Minimally Invasive Direct Coronary Artery Bypass Surgery is significantly shorter and more predictable after total IV anesthesia with remifentanil-propofol than with alfentanil-propofol, which may be important if the goal is that patients will be awakened and tracheally extubated in the operating room.

Aged↗
PubMed2000

The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine.

UNLABELLED: We studied the effect of fluvoxamine and erythromycin on the pharmacokinetics of ropivacaine in a double-blinded, randomized, four-way cross-over study. Eight healthy volunteers ingested daily 1500 mg erythromycin for 6 days, 100 mg fluvoxamine for 5 days (Days 2-6), both erythromycin and fluvoxamine, or placebo. On Day 6, each subject received a single dose of 0.6 mg/kg ropivacaine IV over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'-pipecoloxylidide in venous plasma and urine samples were measured for up to 12 h and 24 h, respectively. Fluvoxamine increased the area under the drug plasma concentration-time curve (AUC) of ropivacaine 3.7-fold (P: < 0.001), prolonged the elimination half-life (t(1/2)) from 2.3 to 7.4 h (P: < 0.01), and decreased the clearance by 77% (P: < 0.001). Erythromycin alone had only a minor effect on the pharmacokinetics of ropivacaine. However, when compared with fluvoxamine alone, the combination of fluvoxamine and erythromycin further increased the area under the drug plasma concentration-time curve and t(1/2) of ropivacaine by 50% (P: < 0.01). We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of ropivacaine. Concomitant use of fluvoxamine and CYP3A4 inhibitor erythromycin further increases plasma ropivacaine concentration by decreasing its clearance. IMPLICATIONS: Clinicians should be aware of the possibility of increased toxicity of ropivacaine when used together with inhibitors of CYP1A2. Concomitant use of CYP1A2 and CYP3A4 inhibitors further increases ropivacaine concentration.

Adult↗
PubMed2000

Intubation and survival in severe paediatric blunt head injury.

The majority of severe childhood injuries are due to head injuries. We studied the impact of emergency intubation in a cohort of children suffering severe blunt head trauma. A 10-year retrospective case note analysis was performed on 176 children (age < 16 years) with severe blunt head trauma (abbreviated injury scale > or =4) in Southern Finland, who required intensive care in a level 1 trauma centre, or who died despite initiation of life supporting measures at the scene. Children in whom emergency intubation was performed either at the scene, or in the emergency room (ER) were analysed. Of the 59 children who fulfilled the study criteria, 20 had an isolated head injury. Most injuries (56/59) were caused by road traffic accidents. Field-intubation was performed in 24 children, and emergency intubation in the ERs of regional hospitals or the level 1 trauma centre, in 13 and 22 children respectively. Mortality was 54.2% (32/59), and was highest in children intubated in regional hospital ERs or in the field. Children intubated at the scene or in the ER of regional hospitals, had significantly worse AIS (head/neck), injury severity score (ISS), and Glasgow coma (GCS) scores than those children intubated in the ER of the level 1 trauma centre. Survival was better in field-intubated children compared with those intubated in regional hospital ERs, despite similar trauma scores (p = 0.05). It is concluded that although children with severe (AIS > or =4) head injury who require emergency intubation have a high overall mortality, field-intubation may improve survival, compared with 'scoop and run' with BLS airway management and deferred emergency intubation.

Abbreviated Injury Scale↗
PubMed1999

Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam.

OBJECTIVE: To assess the effect of human immunodeficiency virus protease inhibitor saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. METHODS: In a double-blind, randomized, two-phase crossover study, 12 healthy volunteers (six men and six women; age range, 21 to 32 years) received oral doses of either 1200 mg saquinavir (Fortovase soft-gel capsule formulation) or placebo three times a day for 5 days. On day 3, six subjects were given 7.5 mg oral midazolam and the other six subjects received 0.05 mg/kg intravenous midazolam. On day 5, the subjects who had received oral midazolam on day 3 received intravenously midazolam and vice versa. Plasma concentrations of midazolam, alpha-hydroxymidazolam, and saquinavir were determined for 18 hours after midazolam administration, and midazolam effects were measured up to 7 hours by six psychomotor tests. RESULTS: Saquinavir increased the bioavailability of oral midazolam from 41% to 90% (P < .005), the peak midazolam plasma concentration more than twofold, and the area under plasma concentration-time curve more than fivefold (P < .001). During saquinavir treatment, five of the six psychomotor tests revealed impaired skills and increased sedative effects after midazolam ingestion (P < .05). Saquinavir decreased the clearance of intravenous midazolam by 56% (P < .001) and increased its elimination half-life from 4.1 to 9.5 hours (P < .01). After intravenous midazolam, only the subjective feeling of drug effect was increased significantly (P < .05) by saquinavir. CONCLUSION: The dose of oral midazolam should be greatly reduced or avoided with saquinavir, but bolus doses of intravenous midazolam can probably be used quite safely. During a prolonged midazolam infusion, an initial dose reduction of 50% followed by careful titration is recommended to counteract the reduced clearance caused by saquinavir.

Administration, Oral↗
PubMed1999

A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol.

BACKGROUND: Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question--are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol? METHODS: Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable. RESULTS: In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%). CONCLUSION: Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.

Adolescent↗