Incidence of propofol infusion syndrome during noninvasive radiofrequency ablation for atrial flutter or fibrillation

BACKGROUND: Propofol infusion syndrome is first manifest by unexplained metabolic acidosis. Its incidence is unknown. METHODS: Charts of all patients undergoing nonsurgical, catheter radiofrequency ablation for atrial flutter or fibrillation from 1999 through 2001 at Mayo Clinic Rochester, who received propofol and had an arterial blood gas drawn during the procedure, were reviewed retrospectively for metabolic acidosis, prospectively defined as base excess -2 or less. Of 301 radiofrequency ablation cases, 55 had an arterial blood gas. Virtually all radiofrequency ablation patients received propofol, so they could not be used as nonpropofol controls. Instead, all carotid endarterectomy patients in 2000 who did not receive propofol and had an arterial blood gas drawn after anesthetic induction and before surgical incision were used as a comparator group. RESULTS: In propofol radiofrequency ablation patients with no apparent cause of metabolic acidosis besides propofol, 13 of 55 (24%) had base excess of -2 or less, versus 22 of 267 carotid patients (8.2%) (P<0.01). Maximal negative base excess was -4.2+/-1.7 in these propofol patients and was not correlated with propofol dose, age, or fluid dose, versus base excess of -3.2+/-1.5 in carotid patients (P>0.05). Propofol patients received prolonged anesthetics (7 h) and high-dose propofol (20 mg/kg). CONCLUSIONS: This is the first incidence estimate of metabolic acidosis during prolonged propofol infusion and suggests that it is not rare. The study is limited by its retrospective nature and by the lack of baseline arterial blood gas data and will require confirmation by prospective study.     

Bispectral index in patients with target-controlled or manually-controlled infusion of propofol

In this prospective, randomized study we compared bispectral index (BIS), hemodynamics, time to extubation, and the costs of target-controlled infusion (TCI) and manually-controlled infusion (MCI) of propofol. Forty patients undergoing first-time implantation of a cardioverter-defibrillator were included. Anesthesia was performed with remifentanil (0.2-0.3 micro g. kg(-1). min(-1)) and propofol. Propofol was used as TCI (plasma target concentration, 2.5-3.5 micro g/mL; n = 20) or MCI (3.0-4.0 mg. kg(-1). h(-1); n = 20). BIS, heart rate, and arterial blood pressure were measured at six data points: T1, before anesthesia; T2, after intubation; T3, after skin incision; T4, after first defibrillation; T5, after third defibrillation; and T6, after extubation. There were no significant hemodynamic differences between the two groups. BIS was significantly lower at T3 and T4 in the TCI group than in the MCI group. The mean dose of propofol was larger in TCI patients (5.8 +/- 1.4 mg. kg(-1). h(-1)) than in the MCI patients (3.7 +/- 0.6 mg. kg(-1). h(-1)) (P < 0.05), whereas doses of remifentanil did not differ. Time to extubation did not differ between the two groups (TCI, 13.7 +/- 5.3 min; MCI, 12.3 +/- 3.5 min). One patient in the MCI group had signs of intraoperative awareness without explicit memory after first defibrillation (BIS before shock, 49; after shock, 83). Costs were significantly less in the MCI group (34.83 US dollars) than in the TCI group (39.73 US dollars). BIS failed to predict the adequacy of anesthesia for the next painful stimulus. IMPLICATIONS: In this prospective, randomized study, bispectral index (BIS), hemodynamics, time to extubation, and costs of target-controlled infusion (TCI) and manually-controlled infusion of propofol were compared. TCI increased the amount of propofol used. BIS failed to predict the adequacy of anesthesia for the next painful stimulus.     

Propofol-nitrous oxide anesthesia enhances the heart rate response to intravenous isoproterenol infusion

Heart rate (HR) response to IV atropine is attenuated during propofol-nitrous oxide (N(2)O) anesthesia. We studied the effects of propofol-N(2)O anesthesia on isoproterenol-induced HR changes. The control group (n = 15) received no propofol and no N(2)O. Patients in the propofol-N(2)O group (n = 21) received IV propofol 2.5 mg/kg over 1 min followed by a continuous infusion of propofol 10 mg x kg(-1) x h(-1). After tracheal intubation, anesthesia was maintained with propofol 5 mg. kg(-1) x h(-1) and 67% N(2)O in oxygen. All patients in both groups received IV isoproterenol at incremental infusion rates (2.5, 5, 7.5, 10, 12.5, 15, and 17.5 ng x kg(-1) x min(-1) for 2 min at each dose) until HR increased more than 20 bpm from baseline values. At the end of each infusion period, hemodynamic data were collected. The HR response to isoproterenol 7.5 ng. kg(-1) x min(-1) was increased more in the propofol group than in the control group (20 +/- 5 versus 14 +/- 4 bpm; P < 0.05). During the isoproterenol infusion at 10 ng. kg(-1) x min(-1), HR increased by more than 20 bpm in all patients in the propofol group but in only 31% of patients in the control group (P < 0.0001). These results suggest that continuous isoproterenol infusion might be useful when a large dose of atropine is ineffective in restoring normal HR during propofol-N(2)O anesthesia. IMPLICATIONS: We demonstrated that the heart rate response to IV isoproterenol infusion is enhanced during propofol-nitrous oxide anesthesia. This suggests that continuous isoproterenol infusion may be useful when a large dose of atropine is ineffective for restoration of normal heart rate in patients receiving propofol-nitrous oxide anesthesia.     

Electroencephalograph variables, drug concentrations and sedation scores in children emerging from propofol infusion anaesthesia

BACKGROUND: Inadequate sedation or oversedation are common problems in Paediatric Intensive Care because of wide variations in drug response and the lack of objective tests for sedative depth. We undertook a pilot study to try to identify correlates of propofol drug concentration, electroencephalographic (EEG) variables and observed behaviour during a stepwise reduction in propofol infusion after paediatric cardiac surgery. METHODS: This was a prospective pilot study with 10 children (5 months to 8 years) emerging from propofol anaesthesia following cardiac surgery with cardiopulmonary bypass (CPB). Patients underwent a stepped wake-up from propofol anaesthesia during which the propofol infusion rate was decreased from 4 mg.kg(-1).h(-1) in 1 mg.kg(-1).h(-1) steps at 30 min intervals. EEG variables, propofol blood concentrations and clinical sedation scores (COMFORT scale) were recorded during the stepped wakeup. Analgesia was maintained with a standardized continuous infusion of fentanyl. RESULTS: : Mean (SD) whole blood propofol concentrations at arousal varied considerably [973 ng.ml(-1) (SD 523 ng.ml(-1))]. The summed ratio (SR) of high frequency to low frequency bands correlated with both propofol infusion rate (R2 value=0.47) and propofol blood concentrations (R2 value=0.64). The mean SR in deeply sedated patients was significantly different from that in the 5 min prior to wakening (6.84 vs 1.55, P=0.00002). There was no relationship between COMFORT scores and SR. CONCLUSIONS: In this group of patients receiving opioid analgesia and relatively high doses of propofol, sedation scores were unhelpful in predicting arousal. The SR correlated with propofol blood concentrations and clinical arousal and may have potential as a predictive tool for arousal in children.     

The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs.

Diaphragmatic fatigue may contribute to the development of respiratory failure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug; Group 2 was infused with small-dose propofol (0.1 mg/kg initial dose plus 1.5 mg x kg(-1) x h(-1) maintenance dose); Group 3 was infused with large-dose propofol (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of propofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). Compared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05) during propofol administration in Groups 2 and 3. The decrease in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that propofol decreases the contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Propofol is a widely used IV anesthetic for the induction and maintenance of general anesthesia and sedation. It decreases, in a dose-related fashion, the contractility of fatigued diaphragm in dogs.     

Death after re-exposure to propofol in a 3-year-old child: a case report

This case report discusses the cause of death in a 3-year-old child who survived a high dose (20 mg x kg-1 x h-1) of propofol, infused over a period of 15 h, following which the patient developed a combined respiratory and metabolic acidosis, the oxygenation remaining normal. Bronchospasm was assumed to be the cause of hypercapnia. At this time the doctors in charge did not think of a possible side-effect of propofol. The administration of propofol was interrupted, the patient recovered within 13 h from the acidosis, woke up and required further sedation. A supposedly entirely safe infusion of 4 mg x kg-1 x h-1 propofol, as recommended in the literature for up to 48 h, was administered. After only 8 h intractable bradycardic dysrhythmias occurred. Although pharmacokinetic studies have pointed to a possible accumulation of propofol during continuous infusions, an interruption of an infusion for several hours has been considered sufficient for practically total clearance of the drug from the body. In this case re-exposure with a recommended dose of propofol was accompanied by bradycardia and dysrythmias that proved to be resistant to therapy and led to fatal cardiac insufficiency with a functioning artificial pacemaker in place. This case raises concerns about the safety of long-term infusions of propofol for sedation in children and possibly also in adults.     

异丙酚对急性和慢性代谢性酸中毒大鼠红细胞内pH的影响

目的 观察异丙酚对急性和慢性代谢性酸中毒大鼠红细胞内pH(pHi)的影响.方法 Wistar大鼠,雌雄不拘.第一部分采用静脉输注HCl的方法制备急性代谢性酸中毒模型,模型制备成功的40只大鼠随机分为4组(n=10):10%脂肪乳10 ml·kg·h-1组(F组)、碳酸酐酶(CA)抑制剂乙酰唑胺20 mg·kg·h-1组(Z组)、异丙酚10 mg·kg·h-1组(P1组)和异丙酚20 mg·kg·h-1组(P2组).第二部分采用管饲NH4Cl的方法制备慢性代谢性酸中毒模型,模型制备成功的40只大鼠随机分为4组(n=10),处理情况同第一部分.分别于给药前、给药1、3、6 h时采集动脉血样,测定红细胞pHi、CA活性及钠氢交换体-1(NHE-1)活性.结果 第一部分与F组比较,Z组CA活性降低(P<0.05或0.01),P1组和P2组pHi、CA活性及NHE-1活性差异无统计学意义(P>0.05).第二部分与F组比较,Z组、P1组和P2组pHi和CA活性降低(P<0.05或0.01);与Z组比较,P1组和P2组pHi和CA活性降低(P<0.05或0.01),NHE-1活性差异无统计学意义(P>0.05).结论 静脉输注异丙酚10、20 mg·kg-1·h-1可导致慢性代谢性酸中毒大鼠红细胞phi降低,其机制与抑制CA活性有关;而对急性代谢性酸中毒大鼠红细胞pHi无影响.     

Lactic acidosis associated with propofol during general anaesthesia for neurosurgery

Propofol infusion syndrome (PRIS) is a new clinical entity reported in critically ill patients. Lactic acidosis, cardiac failure and rhabdomyolysis are the features. Lactic acidosis related to short-term propofol administration has been described during general anaesthesia. Lactic acidosis could be an early marker of PRIS. We report here a case of very early lactic acidosis in a 66-year-old-man receiving propofol during a neurosurgery. The outcome was good after discontinuation of propofol.     

Propofol infusion for the maintenance of short-term anesthesia

The administration of propofol by infusion for maintenance of anesthesia has attracted much attention recently. We investigated the necessary infusion rate of propofol to maintain anesthesia for short surgical procedures without loss of the evident advantages of this substance. Forty unpremedicated female patients aged 18-59, scheduled for minor gynecological procedures, were randomly assigned to four groups. Anesthesia was induced with 2.0 mg/kg propofol i.v. and simultaneously an infusion of 0.05, 0.10, 0.15, or 0.20 mg propofol/kg per minute was started. The patients were breathing N2O/O2 with FIO2 33%. Additional propofol was administered as a bolus of 10 to 20 mg when the patients moved. With 0.05 mg propofol/kg per minute all patients required additional bolus injections of propofol; with 0.10 mg 8 patients, with 0.15 mg 5 patients, and with 0.20 mg 1 patient required bolus injection. Therefore, 0.15 mg/kg per minute can be considered as an approximate ED50 value. The total propofol consumption (infusion + bolus) increased from 0.102 +/- 0.028 (+/- SD) with the lowest infusion rate to 0.202 +/- 0.006 mg/kg per minute with the highest infusion rate and recovery time from 5.2 +/- 1.4 to 9.9 +/- 2.6 min. There was a significant correlation between propofol consumption and recovery time. After induction, arterial blood pressure decreased by systolic/diastolic 20/10-15 mmHg. With the low infusion rate, arterial pressure increased to its control value during operation; it remained at the postinduction value with high infusion rates. Side-effects: 10 patients had salivation that in some instances lead to coughing, 9 reported pain at the injection site during induction, and 9 reported dreams of a pleasant nature.(ABSTRACT TRUNCATED AT 250 WORDS)     

术中静脉输注不同剂量异丙酚对患者酸碱平衡及脂质代谢的影响

目的 评价术中静脉输注不同剂量异丙酚对患者酸碱平衡及脂质代谢的影响.方法 拟行广泛全子宫加盆腔淋巴结清扫术的宫颈癌患者60例,年龄30～64岁,体重40～75 kg,ASA Ⅰ或Ⅱ级,随机分为3组(n=20),Ⅰ组、Ⅱ组和Ⅲ组分别静脉输注异丙酚50、100、150μg·kg~(-1)·min~(-1).分别于麻醉诱导前即刻、开始静脉输注后1、2、3 h及术毕时行动脉血气分析,记录pH值、总二氧化碳(TCO_2)、碱剩余(BE)、HCO_3~-及乳酸(LA)浓度;取颈内静脉血样2 ml测定血清甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDLL-C)、载脂蛋白A_1(APOA_1)及载脂蛋白B(APOB)的浓度.结果 3组各指标均在正常范围内.与麻醉诱导前即刻比较,静脉输注异丙酚后3组pH值、TC_2、BE、HCO_3~-及APOA_1浓度降低,LA及TG浓度升高,Ⅱ组及Ⅲ组LDL-C浓度降低,Ⅲ组APOB浓度降低(P<0.05或0.01);与Ⅰ组比较,静脉输注异丙酚后Ⅱ组及Ⅲ组pH值、BE、LDL-C及APOB浓度降低,TG浓度升高,Ⅲ组TCO_2、HCO_3~、TC及APOA_1浓度降低(P<0.05或0.01);与Ⅱ组比较,静脉输注异丙酚后Ⅲ组pH值、TCO_2、BE、TC及APOB浓度降低,TG浓度升高(P<0.05或0.01).结论 短时静脉输注异丙酚时患者酸碱平衡及脂质代谢均在正常范围,但有发生代谢性酸中毒及脂质代谢异常的趋势,且与剂量有关.     

Propofol infusion syndrome

The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l(-1)), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. There is an association between PRIS and propofol infusions at doses higher than 4 mg.kg(-1).h(-1) for greater than 48 h duration. Sixty-one patients with PRIS have been recorded in the literature, with deaths in 20 paediatric and 18 adult patients. Seven of these patients (four paediatric and three adult patients) developed PRIS during anaesthesia. It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. An early sign of cardiac instability associated with the syndrome is the development of right bundle branch block with convex-curved ('coved type') ST elevation in the right praecordial leads (V1 to V3) of the electrocardiogram. Predisposing factors include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Treatment options are limited. Haemodialysis or haemoperfusion with cardiorespiratory support has been the most successful treatment.     

Dose-response relationship of propofol on mid-latency auditory evoked potentials (MLAEP) in cardiac surgery

BACKGROUND: Propofol-sufentanil anaesthesia has become popular during cardiac surgery for its titrability and short recovery time. Avoidance of awareness is a major goal during cardiac surgery. We therefore investigated the dose-response relationship of propofol and cortical responses (mid-latency auditory evoked potentials, MLAEP). METHODS: One hundred patients undergoing cardiac surgery were investigated. Basic anaesthesia was performed with sufentanil (4.5 microg kg(-1) h(-1)) / flunitrazepam (9 microg kg(-1) h(-1)) infusion (control group); the other groups received in addition a loading dose of propofol 2 mg kg(-1) and a maintainance infusion of 1-3.5 mg kg(-1) h(-1). MLAEP were evaluated by using Pa/Nb-amplitudes and Nb-latencies. Haemodynamics were monitored by ECG, arterial blood pressure and cardiac function with pulmonary artery catheterization. RESULTS: In the control group, median amplitude of MLAEP decreased by 50% with a wide range, but were detectable in >90% of patients throughout surgery. Propofol suppressed amplitude Pa/Nb of MLAEP dose dependently. With 3.5 mg kg(-1) h(-1) amplitudes disappeared in >40% of patients throughout cardiac surgery. Median Nb-latencies increased in the control group from 44 to a range from 50 to 60 ms. In groups with propofol >2 mg kg(-1) h(-1), Nb-latencies, detectable in the patients without complete suppression of MLAEP, increased to median 60 ms. Haemodynamic parameters and cardiac function did not differ among the groups. The use of vasopressors was not increased even with the highest propofol dose used. CONCLUSION: The dose-response effect of propofol on auditory evoked potentials reveals that combining a loading dose of 2 mg kg-1 with a consecutive infusion of 3.5 mg kg(-1) h(-1) significantly suppresses MLAEP during cardiac surgery. Thus, auditory information may not be processed and awareness with recall becomes unlikely.     

Is total body weight an appropriate predictor for propofol maintenance dose?

BACKGROUND: Infusion rate of propofol during anaesthesia is usually based on total body weight. In this study, we have determined the relationship between total body weight and plasma propofol levels when the infusion rate was based on total body weight. METHODS: Sixty patients undergoing elective surgery were studied. Anaesthesia was induced with propofol 1 mg x kg(-1), ketamine 1 mg x kg(-1) and fentanyl 2 microg x kg(-1), and maintained with propofol 5 mg x kg(-1) x h(-1), ketamine 0.5-1 mg x kg(1) x h(-1) and fentanyl 5-15 microg x kg(-1). Propofol infusion rate did not change during anaesthesia, and infusion was terminated at the end of surgery. Immediately prior to termination of the propofol infusion, arterial blood (5 ml) was collected to measure plasma level of propofol by a high-performance liquid chromatography equipped with electrochemical detection. RESULTS: There was a significant correlation between plasma propofol and total body weight (r=0.646, P<0.001). Plasma propofol concentration also correlated with infusion rate, corrected to lean body mass (r=0.527, P<0.001). CONCLUSION: During a fixed infusion rate, plasma propofol concentration may be dependent on total body weight.     

Gender differences in the pharmacokinetics of propofol in elderly patients during and after continuous infusion

Differences in the pharmacokinetics of propofol between male and female patients during and after continuous infusion have not been described in detail in patients aged 65 yr and older. To increase our insight into the pharmacokinetics of propofol in this patient population and to obtain pharmacokinetic parameters applicable in target controlled infusion (TCI), the pharmacokinetics of propofol during and after continuous infusion were studied in 31 ASA class 1 and 2 patients, aged 65-91 yr, scheduled for general surgery. Patients received propofol 1.5 mg kg(-1) i.v. in 1 min followed by 7 mg kg(-1) h(-1) until skin closure in the presence of a variable rate infusion of alfentanil during oxygen-air ventilation. On the basis of arterial blood samples that were taken up to 24 h post-infusion, the pharmacokinetics of propofol were evaluated in a two-stage manner. Multiple linear regression analysis was used to explore the effect of age, weight, gender and lean body mass as covariates. Gender significantly affected the pharmacokinetics of propofol. V3, Cl1 and Cl2 were significantly different between male and female patients, weight only affected Cl1. The pharmacokinetic parameters were: V1=4.88 litre, V2=24.50 litre, V3 (litre)=115+147 x gender (gender: male=1, female=2), Cl1 (litre min(-1))=-0.29+0.022 x weight+0.22 x gender, Cl2 (litre min(-1))=2.84-0.65 x gender (male=1, female=2), and Cl3=0.788 litre min(-1).     

Effect of low-dose propofol infusion on total-body oxygen consumption after coronary artery surgery

OBJECTIVE: To investigate the effect of low-dose propofol infusion on total-body oxygen consumption (VO2) after coronary artery bypass grafting (CABG) surgery. DESIGN: A prospective, randomized, placebo-controlled, double-blind study. SETTING: Cardiovascular intensive care unit in a university hospital. PARTICIPANTS: Thirty patients after elective, uncomplicated CABG surgery. INTERVENTION: Patients were administered a continuous infusion of propofol with a fixed rate of 1 mg/kg/h (n = 15) or placebo (n = 15) during the spontaneous rewarming period of approximately 5 hours after surgery. A light level of sedation (Ramsay sedation score > or =2) was maintained by administering small doses of diazepam, 0.1 mg/kg, as required. Morphine, 0.05 mg/kg, was administered for analgesia as required. MEASUREMENTS AND MAIN RESULTS: Total-body VO2 was measured by indirect calorimetry. In addition, shivering (on a five-grade scale), hemodynamics, and plasma catecholamine and serum cortisol concentrations were measured. Diazepam, 5.6+/-7.4 mg (mean +/- standard deviation), was administered to the patients receiving propofol, and 16.1+/-12.2 mg was administered to the patients receiving placebo (p < 0.05). There was no difference in the dose of morphine between the groups (3.2+/-3.9 v 4.2+/-5.5 mg in the propofol and placebo groups, respectively). At any time during the study, VO2 was not different between the groups. VO2 increased from 130+/-29 to 172+/-29 mL/min/m2 in the propofol group and from 118+/-24 to 167+/-27 mL/min/m2 in the placebo group. Mean arterial pressure and heart rate were lower in the propofol group (p < 0.05). Stress hormone levels did not differ between the groups. CONCLUSION: Low-dose propofol infusion and additional diazepam as required does not decrease total-body VO2 compared with a pure diazepam bolus-dose technique when administered for light sedation during the immediate recovery period after CABG surgery.     

Influence of cardiac output on plasma propofol concentrations during constant infusion in swine

BACKGROUND: As propofol is a high-clearance drug, plasma propofol concentrations can be influenced by cardiac output (CO), which can easily change in response to several factors. If propofol is metabolized in the lungs, the difference between pulmonary and arterial propofol concentrations might also be affected by CO. The objective of the current study was to assess how much plasma propofol concentrations are affected by CO and to determine how much the lungs take part in propofol elimination and in concentration changes affected by CO in anesthetized swine. METHODS: Thirteen swine were studied. Propofol was administered via a peripheral vein at a rate of 6 mg x kg(-1) x h(- 1), and blood samples were simultaneously collected from pulmonary and femoral arteries at 0, 2, 3.5, 5, 7, 10, 20, and 30 min and at 20-min intervals up to 270 min. After 90 min of sampling (baseline 1), CO increased in response to a continuous infusion of dobutamine (20 microg x kg(-1) x min(- 1); high-CO state); the infusion was then stopped, and CO was allowed to return to baseline (baseline 2). Finally, CO decreased with the administration of propranolol (2.0-4.0 mg administered intravenously; low-CO state). Each hemodynamic status was maintained for 1 h. RESULTS: As CO increased 36% from baseline 1, plasma propofol concentrations decreased by 18% from baseline 1, and as CO decreased 42% from baseline 1, plasma propofol concentrations increased by 70% from baseline 1. Plasma propofol concentrations can be expressed by the following equation: plasma propofol concentration (micrograms per milliliter) = 6.51/CO (l/min) + 1.11 (r = 0.78, P < 0.0001). No significant differences were observed between plasma propofol concentrations in pulmonary and femoral arteries in any state, and CO caused no apparent differences between pulmonary and arterial propofol concentrations. CONCLUSIONS: An inverse relation was observed between CO and propofol concentrations. The lungs appear to have a minor effect on plasma propofol concentrations during constant infusion in anesthetized swine.     

Propofol suppresses the cortical somatosensory evoked potential in rats

The dose-response curve for the effect of volatile anesthetics on the somatosensory evoked potential (SEP) is well described, but for propofol, the large dose segment of the curve is undefined. We describe the effect of increasing plasma concentrations of propofol on cortical SEPs in 18 rats. After surgical preparation under ketamine anesthesia, a remifentanil infusion was begun at 2.5, 5, or 10 microg x kg(-1) x min(-1). After 20 min, the propofol infusion was initiated at 20 mg x kg(-1) x h(-1) and was increased to 40, 60, and 80 mg x kg(-1) x h(-1) at 20-min intervals. SEP was recorded before remifentanil infusion, before propofol infusion rate changes, and 30 min after discontinuing propofol infusion. In six additional rats, the plasma concentrations of propofol after each 20-min infusion were measured using gas chromatography. Remifentanil did not have a significant effect, but propofol significantly depressed the SEP amplitude and prolonged the latency at infusion rates of 40 mg x kg(-1) x h(-1) and more. Propofol's effect was dose-dependent, but even at 80 mg x kg(-1) x h(-1) with an estimated plasma concentration of 31.6 +/- 3.4 microg/mL (10.8 50% effective concentration), a measurable response was present in 44.5% of rats. These results suggest that even at large doses, propofol and remifentanil provide adequate conditions for SEP monitoring. IMPLICATIONS: Rats demonstrate dose-dependent somatosensory evoked potential (SEP) suppression with propofol but not with remifentanil. However, SEP suppression by 50% occurred only at large (1.5 EC(50)) concentrations of propofol, and a measurable SEP was present in 8 of 18 rats, even at 10.8 EC(50).     

Propofol and alfentanil infusion

In 42 patients undergoing major surgery, anaesthesia was induced by intravenous alfentanil 10 micrograms/kg together with methohexitone 1.5 mg/kg or propofol 2 mg/kg. An infusion of six times these doses per hour was then started; the rate was varied subsequently as indicated by the monitoring of arterial blood pressure, heart rate, EEG and frontalis electromyogram. The mean duration of infusion was 76.7 minutes for propofol and 74.5 minutes for methohexitone and the infusion was stopped about 10 minutes before the end of surgery in each group. The induction dose differed, but the total dose requirement for the two drugs was similar. In every case, anaesthesia was satisfactory. Methohexitone caused a significant rise in mean pulse rate throughout anaesthesia (p less than 0.05, paired t-test). There was no change in mean pulse rate during propofol infusion. The dose of alfentanil used provided excellent control of autonomic reflexes, with negligible respiratory depression. Naloxone was not required. Propofol provided better anaesthesia than methohexitone, with fewer side effects (p less than 0.05, Chi squared test), easier control of the level of narcosis and faster recovery (p less than 0.001, t-test after log transformation).     

Intravenous magnesium sulfate administration reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia: part I: comparing propofol requirements according to hemodynamic responses: part II: comparing bispectral index in control and magnesium groups

BACKGROUND: The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia. METHODS: Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg x kg(-1) x h(-1)). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 microg x kg(-1) x min(-1) (magnesium group) and 160 microg x kg(-1) x min(-1) (control group), bispectral index (BIS) values were measured. RESULTS: Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 microg x kg(-1) x min(-1)) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32). CONCLUSION: Intravenous administration of magnesium sulfate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anesthesia or analgesia and may be a useful adjunct to propofol anesthesia.     

Pharmacokinetics of propofol infusions in critically ill neonates,infants, and children in an intensive care unit

BACKGROUND: Propofol is a commonly used anesthetic induction agent in pediatric anesthesia that, until recently, was used with caution as an intravenous infusion agent for sedation in pediatric intensive care. Few data have described propofol kinetics in critically ill children. METHODS: Twenty-one critically ill ventilated children aged 1 week to 12 yr were sedated with 4-6 mg. kg(-1).h(-1) of 2% propofol for up to 28 h, combined with a constant morphine infusion. Whole blood concentration of propofol was measured at steady state and for 24 h after infusion using high-performance liquid chromatography. RESULTS: A propofol infusion rate of 4 mg. kg(-1).h(-1) achieved adequate sedation scores in 17 of 20 patients. In 2 patients the dose was reduced because of hypotension, and 1 patient was withdrawn from the study because of a increasing metabolic acidosis. Mixed-effects population models were fitted to the blood propofol concentration data. The pharmacokinetics were best described by a three-compartment model. Weight was a significant covariate for all structural model parameters; Cl, Q2, Q3, V1, and V2 were proportional to weight. Estimates for these parameters were 30.2, 16.0, and 13.3 ml. kg(-1).min(-1) and 0.584 and 1.36 l/kg, respectively. The volume of the remaining peripheral compartment, V3, had a constant component (103 l) plus an additional weight-related component (5.67 l/kg). Values for Cl were reduced (typically by 26%) in children who had undergone cardiac surgery. CONCLUSIONS: Propofol kinetics are altered in very small babies and in children recovering from cardiac surgery. Increased peripheral distribution volume and reduced metabolic clearance following surgery causes prolonged elimination.