Propofol Infusion Rate Research Articles

Outpatient arthroscopic knee surgery under combined local and intravenous propofol anesthesia in children and adolescents

This prospective observational study included a case series of children and adolescents receiving light intravenous propofol anesthesia combined with local anesthesia (LA) for arthroscopic knee procedures. The aim was to examine the merits of anesthesia, to discuss the indications for the procedure and to analyze recovery/discharge times from the postanesthesia care unit (PACU). A cohort of 147 children and adolescents (ASA 1 and 2) aged 12-18 years admitted for outpatient arthroscopic knee procedures between January 2004 and May 2005 were studied. After IV access in the operating theater, the patients received propofol (10 mg.ml(-1)). Arthroscopy was performed approximately 15 min after injecting local anesthetic (15 ml 2% lidocaine with epinephrine 1:200,000) partly at the site of insertion of the arthroscope and other instruments (5 ml), and the rest intra-articular. The following parameters were assessed: airway patency, propofol requirement, vital signs, procedure time, surgical operating conditions, patient satisfaction score, time to discharge, postoperative analgesia and adverse events. Of 147 patients, 133 patients (90.5%) underwent arthroscopic knee surgery, whereas knee arthroscopy alone was performed in 14 patients (9.5%) without indication for operative treatment. The arthroscopy was well tolerated in 96.6% patients (no pain, movement or discomfort during the procedure) and only five patients required conversion to general anesthesia. Pain experienced during the injection of lidocaine was more severe than pain experienced during the surgical procedure itself (P < 0.001). The surgical evaluation of operative conditions (visualization and access to intra-articular structures) was generally satisfactory and completely acceptable. Almost 94% (138/147) of patients said they would have the same procedure again under the same type of anesthesia. The mean propfol induction dose was 1.4 mg.kg(-1) (range: 0.9-3.8) and mean propofol infusion rate 167 microg.kg(-1).min(-1) (range: 130-250). Movement was more likely at lower infusion rates (mean: 151 microg.kg(-1).min(-1)). The maximal decrease in respiratory rate was 5.9 +/- 5.1 br.min(-1) (27.2 +/- 21%) and no patient became hypoxic. Patients recovered to preoperative values at 9.8 +/- 7.5 min following infusion discontinuation. There were no respiratory or cardiovascular complications. The mean stay in PACU was 47 min (range: 32-150). As many as 71% (105/147) of patients required no analgesics during the first two postoperative hours. The combination of light intravenous propofol anesthesia combined with local anesthesia for arthroscopic knee procedures provided effective sedation, good preservation of upper airway patency, rapid recovery and pain relief without major side effects and offers a good alternative to the methods already available. The majority of patients did not require postoperative analgesia.

Tolerance to Propofol’s Sedative Effect in Mechanically Ventilated Rabbits

Propofol is commonly used for the sedation of critically ill patients undergoing mechanical ventilation. These patients may develop tolerance during long-term administration. Here, we describe the development of tolerance to propofol's sedative effect in rabbits during prolonged mechanical ventilation. Six healthy male New Zealand White rabbits were endotracheally intubated and received propofol by continuous IV infusion to maintain sedation for 48 h. The propofol infusion rate (IR) was adjusted to maintain the desired level of sedation. Assessments of the sedation level were made every 30 min or earlier if there were signs of awakening. Propofol concentrations were measured in arterial plasma after every other IR adjustment, provided there was an adequate level of sedation, using high performance liquid chromatography, and calculations of systemic clearance rates were made. The mortality rate was 100% with a survival period of 30.8 +/- 6.0 h (mean +/- sd). The course of IR adjustments followed a 5-phase pattern: 1) steady IR (mean +/- sd duration; 1.2 +/- 0.6 h), 2) increasing IR (9.4 +/- 5.5 h), 3) steady high-IR (2.3 +/- 1.2 h), 4) decreasing IR (13.7 +/- 1.9 h), and 5) steady low-IR (5.0 +/- 2.7 h). The course of propofol concentrations during the experiment in relation to propofol IR followed a 3-phase pattern: 1) steady concentration with increasing IRs (6.0 +/- 2.7 h), 2) increasing concentrations with increasing IR (5.8 +/- 2.5 h), and 3) increasing concentrations with decreasing IR (18.8 +/- 3.3 h). Propofol systemic clearance rates were progressively increased for 6.0 +/- 2.7 h and then gradually decreased for 24.6 +/- 4.7 h. In conclusion, all rabbits developed tolerance to propofol's sedative effect within the first hours of administration related to changes to the drug's metabolic clearance.

Bispectral-Index-Guided Versus Clinically Guided Remifentanil/Propofol Analgesia/Sedation for Interventional Radiological Procedures: An Observer-Blinded Randomized Study

Patients undergoing potentially painful interventional radiological procedures generally require a combination of analgesia and sedation. This sedation/analgesia should allow the patient to communicate while also remaining calm. Bispectral index (BIS) monitoring could be useful in achieving this. The primary end-point of our study was to compare the percentage time with optimal sedation, defined as Sedation Agitation Scale (SAS) grade 4, between a BIS-guided remifentanil/propofol regimen and a clinically guided regimen in 54 randomly allocated patients. The mean +/- sd percentage time with optimal sedation was significantly longer (P = 0.004) in the BIS group (76.6% +/- 14.7%) than in the SAS group (63.8% +/- 16.4%). There was a significant difference in the weighted mean infusion rates of remifentanil (P = 0.0067) and propofol (P = 0.0075) in the BIS group (0.066 +/- 0.027 microg.kg(-1) . min(-1) 1.59 +/- 0.44 mg.kg(-1) . h(-1)) compared with the SAS group (0.091 +/- 0.036 microg.kg(-1).min(-1) 1.92 +/- 0.43 mg.kg(-1).h(-1)), respectively. BIS values exhibited a temporal correlation to SAS scores (r2 = 0.72). In conclusion, a BIS-guided regimen was more effective than a SAS-guided regimen. The use of BIS resulted in fewer remifentanil and propofol doses. The targeted BIS range of 80-85 provided a sufficient functional level of sedation.

Comparison of the Applicability of Rule-Based and Self-Organizing Fuzzy Logic Controllers for Sedation Control of Intracranial Pressure Pattern in a Neurosurgical Intensive Care Unit

This paper assesses the controller performance of a self-organizing fuzzy logic controller (SOFLC) in comparison with a routine clinical rule-base controller (RBC) for sedation control of intracranial pressure (ICP) pattern. Eleven patients with severe head injury undergoing different neurosurgeries in a neurosurgical intensive care unit (NICU) were divided into two groups. In all cases the sedation control periods lasted 1 h and assessments of propofol infusion rates were made at a frequency of once per 30 s. In the control group of 10 cases selected from 5 patients, a RBC was used, and in the experimental group of 10 cases selected from 6 patients, a self-organizing fuzzy logic controller was used. A SOFLC was derived from a fuzzy logic controller and allowed to generate new rules via self-learning beyond the initial fuzzy rule-base obtained from experts (i.e., neurosurgeons). The performance of the controllers was analyzed using the ICP pattern of sedation for 1 h of control. The results show that a SOFLC can provide a more stable ICP pattern by administering more propofol and changing the rate of delivery more often when rule-base modifications have been considered.

Auditory processing during deep propofol sedation and recovery from unconsciousness

Objective Using evoked potentials, this study investigated effects of deep propofol sedation, and effects of recovery from unconsciousness, on the processing of auditory information with stimuli suited to elicit a physical MMN, and a (music-syntactic) ERAN. Methods Levels of sedation were assessed using the Bispectral Index (BIS) and the Modified Observer's Assessment of Alertness and Sedation Scale (MOAAS). EEG-measurements were performed during wakefulness, deep propofol sedation (MOAAS 2–3, mean BIS=68), and a recovery period. Between deep sedation and recovery period, the infusion rate of propofol was increased to achieve unconsciousness (MOAAS 0–1, mean BIS=35); EEG measurements of recovery period were performed after subjects regained consciousness. Results During deep sedation, the physical MMN was markedly reduced, but still significant. No ERAN was observed in this level. A clear P3a was elicited during deep sedation by those deviants, which were task-relevant during the awake state. As soon as subjects regained consciousness during the recovery period, a normal MMN was elicited. By contrast, the P3a was absent in the recovery period, and the P3b was markedly reduced. Conclusions Results indicate that the auditory sensory memory (as indexed by the physical MMN) is still active, although strongly reduced, during deep sedation (MOAAS 2–3). The presence of the P3a indicates that attention-related processes are still operating during this level. Processes of syntactic analysis appear to be abolished during deep sedation. After propofol-induced anesthesia, the auditory sensory memory appears to operate normal as soon as subjects regain consciousness, whereas the attention-related processes indexed by P3a and P3b are markedly impaired. Significance Results inform about effects of sedative drugs on auditory and attention-related mechanisms. The findings are important because these mechanisms are prerequisites for auditory awareness, auditory learning and memory, as well as language perception during anesthesia.

Bolus Configuration Affects Dose Requirements of Intracarotid Propofol for Electroencephalographic Silence

We hypothesized that an intracarotid bolus injection of propofol to produce electroencephalographic (EEG) silence would require a smaller dose of the drug compared with the continuous infusion of the drug. Furthermore, the bolus propofol dose will be a function of the bolus characteristics in each bolus (mass/volume). We compared the dose requirements of intracarotid propofol needed to maintain EEG silence when delivered as bolus injections to continuous infusions in rabbits. Subsequently, we compared whether four different bolus characteristics (concentration and volume) of propofol (0.33% x 0.1 mL, 0.33% x 0.3 mL, 1% x 0.1 mL, and 1% x 0.3 mL) affected the dose required to produce EEG silence. We found that the infusion rate of propofol required to sustain EEG silence was three-fold larger than the dose required by bolus injections, 22.8 +/- 11.9 vs 6.2 +/- 2.9 mL/h for infusion versus bolus, respectively (n = 7, P < 0.004). Furthermore, during bolus injection, the doses of propofol required to produce EEG silence were a direct function of the bolus volume and the mass of drug in each bolus, total dose = 3.6 + 29 x mg/bolus, n = 32, r = 0.85. For maximum regional effects of the bolus intracarotid drug injection, the bolus characteristics (volume and drug concentration) have to be optimized.

Influence of the Descending Thoracic Aortic Cross Clamping on Bispectral Index Value and Plasma Propofol Concentration in Humans

In this study, the authors investigated changes in Bispectral Index (BIS) values and plasma propofol concentrations (Cp) after aortic cross clamping in the descending thoracic aortic aneurysm repair surgery during propofol anesthesia. Prospectively, in 10 patients undergoing thoracic aortic surgery during total intravenous anesthesia with propofol, BIS values were recorded during cross clamping of the descending thoracic aorta. In this study, the rate of propofol infusion was controlled to keep the BIS value between 30 and 60 throughout surgery. Simultaneously, Cp values in the blood samples taken from the right radial artery (area proximal to cross clamping) and the left femoral artery (area distal to cross clamping) were measured. Approximately 15 min after initiating aortic cross clamping, BIS values in all cases started to decrease abruptly. Cp values of samples taken from the radial artery after cross clamping of the aorta were significantly (P < 0.05) increased compared with pre-cross clamp values (1.8 +/- 0.4 microg/ml), and the mean Cp after aortic cross clamping varied between 3.0 and 5.3 microg/ml. In addition, there were significant differences in the Cp values between radial arterial and femoral arterial blood samples throughout aortic cross clamping. Cp values in samples from the radial artery were approximately two to seven times higher than those from the femoral artery. This study showed that Cp values increased and BIS values decreased rapidly after aortic cross clamping in thoracic aortic aneurysm repair surgery during propofol anesthesia. These findings suggested that all anesthesiologists should control the infusion rate carefully, taking the abrupt changes in its pharmacokinetics into consideration, especially during cross clamping of the descending thoracic aorta.

A comparison of cardiorespiratory variables during isoflurane–fentanyl and propofol–fentanyl anaesthesia for surgery in injured cats

ObjectiveTo compare haemodynamic and respiratory variables during isoflurane–fentanyl (IF) and propofol–fentanyl (PF) anaesthesia for surgery in injured cats. Study designProspective, randomized, controlled clinical study. Animals Thirty-three client-owned injured cats undergoing orthopaedic surgery. Materials and methodsPre-anaesthetic medication was intravenous midazolam 1 mg kg−1, butorphanol 0.4 mg kg−1 and ketamine 2 mg kg−1. Anaesthesia was induced with propofol (P) and maintained with either: (a) a continuous rate infusion (CRI) of fentanyl (F) 0.02 mg kg−1 hour−1 and isoflurane (initial end-tidal concentration of 1%), (b) a fentanyl CRI (dose as before) and sevoflurane (initial end-tidal concentration of 2%) or (c) a CRI of propofol (12 mg kg−1 hour−1). All three techniques were given to effect until surgical anaesthesia was achieved. Heart rate and rhythm (ECG), mean arterial blood pressure, respiratory rate, tidal volume and end-tidal CO2 concentration were recorded. Venous blood gas analysis was performed before and after sedation, and at the end of anaesthesia. Blood chemistry and blood cell counts were assessed before, at the end of, and 24 hours after anaesthesia. The variables recorded from cats anaesthetized with IF and PF were compared. ResultsMean end-expiratory isoflurane concentration was 1.19 ± 0.19%. The propofol infusion rate was 11.4 ± 0.8 mg kg−1 hour−1. No significant differences between the two groups in heart rate were identified; no cardiac dysrhythmias were recorded. Mean arterial blood pressure was significantly lower in IF cats during skin incision (p = 0.01), during surgery without intense surgical stimulation (p < 0.01) and during surgery with intense surgical stimulation (p = 0.01). Nine of 11 cats in the IF group were markedly hypotensive (34–49 mmHg) while seven of 11 cats in group PF were mildly hypotensive (49–59 mmHg). One of 11 cats in group IF and nine of 11 cats in group PF required intermittent positive pressure ventilation (IPPV) to maintain end-tidal CO2 levels below 6.66 kPa (50 mmHg). Conclusion and clinical relevance Despite the necessity to ventilate the lungs of cats in the PF group, arterial blood pressure was better maintained. Propofol–fentanyl anaesthesia is better for surgery in injured cats providing the means to impose IPPV are available.

Evaluation of total intravenous anesthesia with propofol or ketamine-medetomidine-propofol combination in horses

Objective-To compare the anesthetic and cardiorespiratory effects of total IV anesthesia with propofol (P-TIVA) or a ketamine-medetomidine-propofol combination (KMP-TIVA) in horses. Design-Randomized experimental trial. Animals-12 horses. Procedure-Horses received medetomidine (0.005 mg/kg [0.002 mg/lb], IV). Anesthesia was induced with midazolam (0.04 mg/kg [0.018 mg/lb], IV) and ketamine (2.5 mg/kg [1.14 mg/lb], IV). All horses received a loading dose of propofol (0.5 mg/kg [0.23 mg/lb], IV), and 6 horses underwent P-TIVA (propofol infusion). Six horses underwent KMP-TIVA (ketamine [1 mg/kg/h {0.45 mg/lb/h}] and medetomidine [0.00125 mg/kg/h {0.0006 mg/lb/h}] infusion; the rate of propofol infusion was adjusted to maintain anesthesia). Arterial blood pressure and heart rate were monitored. Qualities of anesthetic induction, transition to TIVA, and maintenance of and recovery from anesthesia were evaluated. Results-Administration of KMP IV provided satisfactory anesthesia in horses. Compared with the P-TIVA group, the propofol infusion rate was significantly less in horses undergoing KMP-TIVA (0.14 +/- 0.02 mg/kg/min [0.064 +/- 0.009 mg/lb/min] vs 0.22 +/- 0.03 mg/kg/min [0.1 +/- 0.014 mg/lb/min]). In the KMP-TIVA and P-TIVA groups, anesthesia time was 115 +/- 17 minutes and 112 +/- 11 minutes, respectively, and heart rate and arterial blood pressure were maintained within acceptable limits. There was no significant difference in time to standing after cessation of anesthesia between groups. Recovery from KMP-TIVA and P-TIVA was considered good and satisfactory, respectively. Conclusions and Clinical Relevance-In horses, KMP-TIVA and P-TIVA provided clinically useful anesthesia; the ketamine-medetomidine infusion provided a sparing effect on propofol requirement for maintaining anesthesia.

Discontinuous Monitoring of Propofol Concentrations in Expired Alveolar Gas and in Arterial and Venous Plasma during Artificial Ventilation

Analyzing propofol concentration in expired alveolar gas (cPA) may be considered as a convenient, noninvasive method to follow the propofol concentration in plasma (cPPL). In the current study, the authors established procedures to measure cPA and cPPL for the assessment of their relation in two animal models during anesthesia. Expired alveolar gas and mixed venous and arterial blood were simultaneously sampled during continuous application of propofol for general anesthesia to three goats and three pigs. Propofol infusion rates were varied to modify plasma concentrations. cPA, sampled cumulatively over several respiratory cycles, was quantified by thermal desorption gas chromatography-mass spectrometry. cPPL was determined using reversed phase high-performance liquid chromatography with fluorescence detection. cPA ranged from 0 to 1.4 and from 0 to 22 parts per billion in goats and pigs, respectively, at cPPL of 0-8 microg/ml. The relation between cPA and cPPL was linear; however, the slopes of the regression lines varied between animals. Propofol can be quantified in expired alveolar gas. The results stress the role of marked species-specific variability.

Infusion Pump Delivers Over-Dosage of Propofol as a Result of Missing Syringe Support

We describe the malfunction of a common drug infusion pump. The syringe saddle was missing and allowed the syringe barrel to contact the pump case, which decreased the outward displacement of the syringe clamp. Then, the infusion pump falsely detected a smaller syringe size and consequently delivered an increased infusion rate and overdose of propofol to the patient. More commonly, an incorrectly mounted syringe may increase the outward displacement of the syringe clamp so that the infusion pump falsely detects a larger syringe size, with resultant less than expected infusion rate.

Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome

The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia, and sudden cardiac death after long-term, high-dose propofol infusion has been referred to as propofol infusion syndrome (PRIS). The purpose of this study was to explore the ECG abnormalities observed in a patient with PRIS in order to identify possible pathophysiologic mechanisms of the syndrome. ECG changes in the index case were characterized by down-sloping ST-segment elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We subsequently assessed the relationship between this ECG pattern and the propofol infusion rate, the development of arrhythmias, and the occurrence of sudden death in a previously described cohort of 67 head-injured patients, seven of whom had been identified as having PRIS. Six of the PRIS patients developed the ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of irrecoverable electrical storm. This ECG pattern was the first aberration recorded hours before the death of these patients. ECGs that were available for 30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients developed ventricular arrhythmias. Our findings indicate that development of an acquired Brugada-like ECG pattern in severely head-injured patients is a sign of cardiac electrical instability that predicts imminent cardiac death. Future studies will determine whether such an ECG pattern also predicts imminent cardiac arrhythmia in other patient populations.

Comparison of Remifentanil With Fentanyl for Deep Sedation in Oral Surgery

The aim of this study was to compare recovery for oral surgery patients given a deep sedation regimen of midazolam, propofol, and remifentanil with a standard control of fentanyl in place of remifentanil. This investigation was designed as a randomized, prospective, single-blinded controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1 microg/kg, and propofol initially at 140 microg/kg/min. Group 2 received midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given at an initial propofol infusion rate of 40 microg/kg/min. Outcome measures included time to response to verbal command, Aldrete score = 9, Postanesthesia Discharge Scoring System = 7, and assessment by the Digit Symbol Substitution Test. Forty-seven subjects were entered in the study. Baseline findings were homogenous between the 2 groups. Subjects in group 2 recovered earlier (P < .005) and required less propofol for both the induction (0.8 +/- 0.4 versus 1.2 +/- 0.6 mg/kg; mean +/- SD, P < .01) and maintenance of deep sedation (46 +/- 9 versus 131 +/- 17 microg/kg/min; P < .005). There were minor differences in vital signs. This study demonstrated that this remifentanil regimen provided significantly more rapid recovery and used significantly less propofol compared with the fentanyl regimen.

Effect of Small-Dose Sufentanil: Target-Controlled Infusion Combined with General Anesthesia Using Propofol

Background: Sufentanil has been shown to act synergistically when combined with propofol, or when combined with potent inhalation anesthetics. The aiml of this study was to determine the dosing rate and target plasma concentration of propofol in the presence of low concentrations and to determine the impact of sufentanil infusion. Methods: Sixty patients undergoing a plastic surgery and urologic surgery were anesthetized with nitrous oxide, and given a target-controlled infusion (TCI) of sufentanil [target plasma concentrations of 0 (group 1) and 0.05 ng/ml (group 2)], and propofol at rates varying according to the bispectal index (BIS). The mean target concentration (Tc) and infusion rate of propofol according to the changes in the sufentanil concentrations were determined. The recovery time (from stopping the infusion to eye opening) and side effects were compared. Results: The induction time and recovery time were shorter in group 2 than in group 1 (P 25.2/kg/min, 4.1 0.8/ml) than in group 1 (161.7 26.9/kg/min, 4.7 0.5/ml) (P 0.8/ml and 0.05 ng/ml.

Total intravenous anaesthesia in horses using medetomidine and propofol

ObjectiveTo examine the clinical suitability of medetomidine–propofol infusions for total intravenous anaesthesia in horses. AnimalsFifty client-owned horses of mixed breed, age [mean ± SD (range)] 6.6 ± 4.4 (0.04–18) years, mass 478 ± 168.3 (80–700) kg presented for a range of operations requiring general anaesthesia. Materials and methodsPre-anaesthetic medication was intravenous (IV) medetomidine 7 μg kg−1. Anaesthesia was induced with IV ketamine (2 mg kg−1) and diazepam (0.02 mg kg−1). After endotracheal intubation, O2 was delivered (FiO2 > 0.85). Positive pressure ventilation was initiated if breath-holding in excess of 1 minute occurred. Anaesthesia was maintained with a constant rate medetomidine infusion (3.5 μg kg−1 hour−1) and propofol infused IV to effect (initial dose 0.1 mg kg−1 minute−1). Heart (HR) respiratory (fr) and propofol administration rates, and systemic arterial blood pressures were recorded at 5-minute intervals. Arterial blood gas (O2 and CO2) tensions and pH values were recorded every 15 minutes. Ten minutes after ending medetomidine–propofol infusion, medetomidine (2 μg kg−1; IV) was given. Cardiopulmonary data were analysed using descriptive statistical techniques. ResultsThirty-three orthopaedic, seven integumentary and 10 elective abdominal operations were performed. Cardiopulmonary data, presented as range of mean individual (and absolute individual minimum and maximum values) were: HR: 28.0–39.2 (16–88) beats minute−1; mean arterial blood pressure: 74.0–132.5 (42–189) mmHg; PaO2: 22.1–42.9 (4.9–67.8) kPa; [166–322 (37–508) mmHg], PaCO2: 6.7–8.1 (4.2–11.8) kPa [50–61 (32–88) mmHg] and pH 7.35–7.39 (7.15–7.48). Positive pressure ventilation was required in 23 horses. In three horses, HR values below 20 beats minute−1 were treated with 20 μg kg−1 atropine (IV). Mean propofol infusion rates were 98–108 μg kg−1 minute−1. During anaesthesia, movement occurring in 14 horses was controlled with thiopental. Duration of anaesthesia was 111.6 ± 41.4 (46–225) minutes. Recovery in all horses was uneventful and completed within 42.2 ± 19.8 (12–98) minutes. Conclusions and clinical relevanceMedetomidine–propofol infusion produces adequate conditions for a range of surgical procedures. Cardiovascular function was adequate, as no pressor agents were required. Positive pressure ventilation was required in 23 horses.

Variáveis fisiológicas em cães submetidos à infusão contínua de diferentes doses de propofol

A fim de determinar possíveis alterações nos principais parâmetros fisiológicos determinados pela infusão contínua de propofol, em diferentes doses, foram utilizados 24 cães adultos distribuídos aleatoriamente em 3 grupos (P2, P4 e P8). Os animais foram induzidos à anestesia pela administração intravenosa de propofol (10mg/kg) e, ato contínuo, os cães receberam o anestésico, em infusão contínua nas doses de 0,2mg/kg/min (P2), 0,4mg/kg/min (P4) e 0,8mg/kg/min (P8). As mensurações dos valores das variáveis cardiorrespiratórias [freqüência cardíaca (FC); pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM, respectivamente); eletrocardiografia e freqüência respiratória (f)] e temperatura retal (T) foram realizadas antes da aplicação do fármaco (M0) e após 10, 20, 30, 40 e 50 minutos do início da infusão contínua. Os dados numéricos das variáveis estudadas foram submetidos à Análise de Variância (ANOVA) seguida pelo Teste F (P&lt;0,05). Para FC, observaram-se diferenças entre os grupos no M20 (P2: 91 ± 14,92; P4: 113 ± 17,18; P8: 120 ± 14,84), M30 (P2: 89 ± 13,79; P4: 110 ± 14,3; P8: 114 ± 10,89) e em M40 (P2: 88 ± 17,3; P4: 103 ± 16; P8: 109 ± 8,2), que podem ser justificadas por P2 apresentar menor redução da PAM, não havendo a necessidade de aumento da FC para estabilizar o débito cardíaco e consequentemente para manter a PA. A PAS registrou redução de 26,9% para P2, 23,6% para P4 e 30,6% para P8. Para PAD foram observados decréscimos de 36,2% para P2; 38,1 para P4 e 52,7% para P8, enquanto para PAM a diminuição foi de 32% para P2, 26,3% para P4 e 38,4% para P8. Essas reduções poderiam ser ocasionadas pela diminuição da resistência periférica vascular. Concluiu-se que as reduções ocorridas na PAS, PAD, PAM e f são dependentes da dose de infusão do fármaco, que também proporcionou discreta redução na temperatura retal nos três grupos.

Propofol-Associated Hypertriglyceridemia and Pancreatitis in the Intensive Care Unit: An Analysis of Frequency and Risk Factors

To characterize the frequency, severity, risk factors, and clinician response to propofol-associated hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis. Retrospective analysis. Medical and surgical intensive care units. One hundred fifty-nine adult intensive care patients administered propofol for 24 hours or longer and who had at least one serum triglyceride concentration. Patient records were reviewed to identify the frequency of hypertriglyceridemia (serum triglyceride concentration > or = 400 mg/dl) and pancreatitis (amylase concentration > or = 125 IU/L, lipase concentration > or = 60 IU/L, and abdominal computed tomography scan or clinical examination findings consistent with pancreatitis). Of the 159 patients, 29 (18%) developed hypertriglyceridemia; six (21%) of the 29 had a serum triglyceride concentration of 1000 mg/dl or greater. The median maximum serum triglyceride concentration was 696 mg/dl (range 403-1737 mg/dl). At the time when hypertriglyceridemia was detected, the median infusion rate of propofol was 50 microg/kg/minute (range 5-110 microg/kg/min). The median time from the start of propofol therapy to identification of hypertriglyceridemia was 54 hours (range 14-319 hrs). Propofol was discontinued within 24 hours of detecting the hypertriglyceridemia 84% of the time. Compared with those who did not develop hypertriglyceridemia, patients who developed hypertriglyceridemia were older, had a longer intensive care unit stay, and received propofol for a longer duration; they were also more likely to be admitted to the medical versus the surgical intensive care unit. Pancreatitis developed in three (10%) of the 29 patients with hypertriglyceridemia. Hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis are often seen in intensive care patients receiving propofol. Serum triglyceride concentrations should be routinely monitored in these patients. In addition, alternative sedation strategies should be considered when hypertriglyceridemia is detected.

Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation

Anaesthetics blunt neuronal responses to noxious stimulation, including effects on electroencephalographic (EEG) responses. It is unclear how anaesthetics differ in their ability to modulate noxious stimulation-evoked EEG activation. We investigated the actions of propofol and halothane on EEG responses to noxious stimuli, including repetitive electrical C-fibre stimulation, which normally evokes neuronal wind-up. Rats were anaesthetized with halothane (n=8) or propofol (n=8), at 0.8x or 1.2x the amount required to produce immobility in response to tail clamping [minimum alveolar concentration (MAC) for halothane and median effective dose (ED(50)) for propofol]. We recorded EEG responses to repetitive electrical stimulus trains (delivered to the tail at 0.1, 1 and 3 Hz) as well as supramaximal noxious tail stimulation (clamp; 50 Hz electrical stimulus, each for 30 s). Under halothane anaesthesia, noxious stimuli evoked an EEG activation response manifested by increased spectral edge frequency (SEF) and median edge frequency (MEF). At 0.8 MAC halothane, the tail clamp increased the MEF from approximately 6 to approximately 8.5 Hz, and the SEF from approximately 25.5 to approximately 27 Hz. At both 0.8 and 1.2 MAC halothane, similar patterns of EEG activation were observed with the 1 Hz, 3 Hz and tetanic stimulus trains, but not with 0.1 Hz stimulation, which does not evoke wind-up. Under propofol anaesthesia, noxious stimuli were generally ineffective in causing EEG activation. At 0.8 ED(50) propofol, only the tail clamp and 1 Hz stimuli increased MEF ( approximately 8 to approximately 10-10.5 Hz). At the higher propofol infusion rate (1.2 ED(50)) the repetitive electrical stimuli did not evoke an EEG response, but the tetanic stimulus and the tail clamp paradoxically decreased SEF (from approximately 23 to approximately 21.5 Hz). Propofol has a more significant blunting effect on EEG responses to noxious stimulation compared with halothane.

Development of acute tolerance to the EEG effect of propofol in rats

A previous study in rats with propofol suggested the development of acute tolerance to the EEG effect. The aim of this study was to evaluate acute tolerance by means of EEG-controlled closed-loop anaesthesia as this approach allows precise determination of drug requirement to maintain a defined drug effect. Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were included in the study. The EEG was recorded with occipito-occipital needle electrodes and a modified median frequency (mMEF) of the EEG power spectrum was used as a pharmacodynamic control parameter. The propofol infusion rate was controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3 (0.5) Hz for 90 min. The performance of the closed-loop system was characterized by the prediction error PE=(mMEF-set point)/set point. Plasma propofol concentrations were determined from arterial samples by HPLC. The chosen set point was successfully maintained in all rats. The median (SE) and absolute median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol concentration increased significantly from 2.9 (2.2) microg ml(-1) at the beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg kg(-1) min(-1). The minimum value of the mean arterial pressure during closed-loop administration of propofol was 130 (24) mm Hg, compared with a baseline value of 141 (12) mm Hg. The increase in propofol concentration at constant EEG effect indicates development of acute tolerance to the hypnotic effect of propofol.

Infusão contínua de propofol em gatos pré-medicados com cetamina-midazolam

Estudaram-se os efeitos anestésicos e cardiorrespiratórios produzidos pela infusão contínua de propofol em gatos pré-medicados com a associação cetamina-midazolam. Catorze gatos adultos foram igualmente distribuídos em dois grupos (TX1 e TX3) aos quais administraram-se, pela via intramuscular, cetamina (3,0mg/kg) e midazolam (0,3mg/kg). Decorridos cinco minutos procedeu-se a indução anestésica pela administração intravenosa de propofol (5,0mg/kg), imediatamente seguida pela infusão contínua do agente hipnótico nas doses de 0,1 ou 0,3mg/kg/min, aos animais de TX1 e TX3, respectivamente. Foram mensuradas as freqüências cardíaca e respiratória, temperatura retal, saturação de oxihemoglobina, concentração exalada de dióxido de carbono e pressão arterial. Em TX3 observou-se manutenção de adequado plano anestésico, enquanto que os animais do TX1 apresentaram-se sedados. Houve decréscimo acentuado da freqüência cardíaca, pressão arterial e elevação da concentração de dióxido de carbono exalado no TX3. Conclui-se que o emprego de propofol na dose de infusão de 0,3mg/kg/min em gatos pré-medicados com cetamina-midazolam produz anestesia satisfatória, bradicardia, depressão da função respiratória e pressão arterial.