Low-dose Propofol Research Articles

Effect of a priming dose of propofol immediately before induction on fentanyl-induced cough: A prospective clinical study

Context: It is not uncommon for fentanyl to induce cough at the time of induction. Aims: To evaluate the effect of subhypnotic dose of propofol on the incidence of occurrence and intensity of fentanyl-induced cough (FIC). Settings and Design: This is a prospective, randomized controlled study. Subjects and Methods: A total of 150 patients of the American Society of Anesthesiologists Classes I and II were assigned to one of the two groups: Group A received normal saline as placebo and Group B received low dose propofol (20 mg) before fentanyl given at a dose of 1.5 μg/kg through a peripheral intravenous catheter. The incidence of occurrence and intensity of cough were observed for the two groups. Statistical Analysis Used: One-way ANOVA, Chi-square test, Fisher's exact test, and Mann–Whitney U-test were used for statistical analysis. P Results: The incidence of occurrence of FIC was 29.3% and 6.6%, respectively, for placebo and propofol groups ( P = 0.0000). Further, there was statistically significant difference between the groups for different grades of intensity ( P = 0.032). There were 21% of patients who suffered desaturation and 1.3% chest wall rigidity in placebo group while no such cases were recorded for the propofol group. Conclusions: Subhypnotic dose of propofol can effectively attenuate FIC. It reduces not only the incidence of occurrence but also the intensity of the cough.

Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports.

IntroductionPropofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome.MethodsWe searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality.ResultsKnowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose.ConclusionPRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1112-5) contains supplementary material, which is available to authorized users.

Non-anesthesiologist administration of propofol for gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates Guideline – Updated June 2015

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA). It addresses the administration of propofol by non-anesthesiologists for gastrointestinal (GI) endoscopy. Main Recommendations 1 We recommend that the type of endoscopic procedure and the patient’s American Society of Anesthesiologists (ASA) physical status, age, body mass index, Mallampati’s classification, and risk factors for obstructive sleep apnea (OSA) be assessed before each procedure with non-anesthesiologist administration of propofol (NAAP) (strong recommendation, moderate quality evidence). 2 We suggest primary involvement of an anesthesiologist in patients of ASA class ≥ 3, with a Mallampati’s class ≥ 3 or other conditions that put them at risk of airway obstruction (e. g. pharyngolaryngeal tumors), in patients who chronically receive significant amounts of narcotic analgesics, or in cases where a long-lasting procedure is anticipated (weak recommendation, low quality evidence). 3 We suggest consideration of capnographic monitoring during NAAP in specific situations including high risk patients, intended deep sedation, and long procedures (weak recommendation, high quality evidence). 4 We suggest propofol monotherapy except in particular situations (weak recommendation, high quality evidence). 5 We recommend administering propofol through intermittent bolus infusion or perfusor systems, including target-controlled infusion (TCI), and consideration of patient-controlled sedation (PCS) in particular situations (strong recommendation, high quality evidence). 6 We suggest that patients listen to self-selected music during upper and lower GI endoscopy procedures (weak recommendation, moderate quality evidence). 7 We do not suggest using pharyngeal anesthesia during propofol sedation for upper GI endoscopy (weak recommendation, moderate quality evidence). 8 We suggest using the post-anesthetic discharge scoring system (PADSS) to determine when patient recovery is sufficient to allow discharge (weak recommendation, low quality evidence). 9 Minimum discharge criteria should be fulfilled before discharging a patient. We recommend that patients who have received combined regimens, and all patients of ASA class > 2, should upon discharge be accompanied by a responsible person and refrain for 24 hours from driving, drinking alcohol, operating heavy machinery, or engaging in legally binding decisions. Advice should be provided verbally and in written form to the patient, including a 24-hour contact phone number (strong recommendation, low quality evidence). 10 For patients of ASA classes 1 – 2 who have received low dose propofol monotherapy, a 6-hour limit is suggested (weak recommendation, low quality evidence).

Effects of Propofol on Excitatory and Inhibitory Amino Acid Neurotransmitter Balance in Rats with Neurogenic Pulmonary Edema Induced by Subarachnoid Hemorrhage

Propofol exhibits neuroprotective effects mediated by the inhibition of excitatory amino acid (EAA) neurotransmitter release and potentiation of inhibitory amino acid (IAA) neurotransmitters. To our knowledge, this is the first study to investigate the effects of propofol on the EAA and IAA balance in neurogenic pulmonary edema (NPE). Sixty male Wistar rats were randomized to Sham, NPE, Low-dose propofol, and High-dose propofol groups. NPE was induced via rapid injection of autologous blood (0.5ml) into the cisterna magna. The Low- and High-dose propofol groups were pretreated with boluses of 2 and 5mgkg(-1), respectively, prior to blood injection, followed by continuous propofol infusion at 6 and 15mgkg(-1)h(-1), respectively. The mean arterial pressure (MAP), heart rate, intracranial pressure (ICP), peak inspiratory pressure (PIP), and arterial blood gases were continuously recorded. After 2h, the lung wet-to-dry weight ratio, total protein concentration in the bronchoalveolar lavage fluid (BALF), brain water content, cortical EAA and IAA levels, chest X-ray, and histological staining of lung sections were evaluated. Blood injections into the cisterna magna induced NPE and hemodynamic changes. Propofol alleviated the increases in the MAP, ICP, and PIP, improved oxygenation and histopathological changes, ameliorated pulmonary and cerebral edema, increased the IAA brain levels, and decreased the ratio of Glu to γ-aminobutyric acid. The current findings suggest that propofol improves NPE likely via IAA accumulation and the regulation of EAA and IAA balance, which may represent an effective treatment for NPE.

Propofol differentially inhibits the release of glutamate, γ-aminobutyric acid and glycine in the spinal dorsal horn of rats.

Propofol (2, 6-diisopropylphenol) is an intravenous anesthetic that is commonly used for the general anesthesia. It is well known that the spinal cord is one of the working targets of general anesthesia including propofol. However, there is a lack of investigation of the effects of propofol on spinal dorsal horn which is important for the sensory transmission of nociceptive signals. The objective of this study was to investigate the effects of increasing dosage of propofol on the release of glutamate (Glu), γ-aminobutyric acid (GABA) and glycine (Gly) in the spinal dorsal horn. The efflux of Glu, GABA or Gly in the spinal dorsal horn of rats was detected using transverse spinal microdialysis under an awake condition and various depths of propofol anesthesia. The infusion rates of propofol were, in order, 400 µg/(kg·min), 600 µg/(kg·min) and 800 µg/(kg·min), with a 20 min infusion period being maintained at each infusion rate. Propofol decreased the glutamate efflux within spinal dorsal horn in a dose-dependent manner, and the maximum decrease was 56.8 ± 6.0% at high-dose propofol infusion producing immobility. The inhibitory GABA and Gly efflux was also decreased about 15-20% at low-dose propofol infusion only producing sedation, but did not continue to drop with higher doses of propofol. Propofol decreased both excitatory and inhibitory amino acids efflux in spinal dorsal horn, and the preferential suppression of the excitatory amino acid might be associated with the analgesic effect of propofol.

Propofol Treatment Inhibits Constitutive Apoptosis in Human Primary Neutrophils and Granulocyte-Differentiated Human HL60 Cells.

Apoptosis regulation is essential for neutrophil homeostasis. We previously demonstrated that a process involving glycogen synthase kinase (GSK)-3β determines neutrophil apoptosis. As for this apoptotic process, an overdose of propofol (2,6-Diisopropylphenol; 25 μg/ml or 140 μM) also causes GSK-3β-mediated macrophage apoptosis; however, the early deactivation of GSK-3β with low-dose propofol has been shown. Therefore, we hypothesize that low-dose propofol may induce neutrophil survival via GSK-3β inactivation. Following in vitro culture, the therapeutic concentration of propofol (10 μg/ml or 56 μM) treatment decreased constitutive apoptosis in isolated human primary neutrophils and in granulocyte-differentiated HL60 cells after all-trans retinoic acid (1 μM) treatment. The inactivation of phosphatidylinositol 3-kinase (PI3-kinase)/AKT and the activation of GSK-3β results in myeloid cell leukemia 1 (Mcl-1) down-regulation, the loss of the mitochondrial transmembrane potential, and caspase-3 activation in these cells, which is accompanied by apoptosis. Notably, propofol treatment attenuates these effects in a PI3-kinase-regulated manner. We found that propofol initiates PI3-kinase/AKT-mediated GSK-3β inactivation and Mcl-1 stabilization, rescuing the constitutive apoptosis in primary neutrophils and granulocyte-differentiated acute promyelocytic leukemia HL60 cells.

Propofol alleviates liver oxidative stress via activating Nrf2 pathway

BackgroundNuclear factor-E2–related factor 2 (Nrf2)–mediated antioxidant response is the main protective system of graft-liver against ischemia–reperfusion injury after liver transplantation. Propofol is considered to confer protective effects on different organs; thus, we explored the possibility that whether propofol could attenuate graft-liver injury in a rat autologous orthotopic liver transplantation (AOLT) model and mechanisms were associated with activation of Nrf2 pathway. MethodsSprague–Dawley rats were randomly divided into four groups: sham-operated group, saline-treated AOLT group, low-dose propofol intervention group, and high-dose propofol intervention group. Liver injury was determined, and concentration of hydroxyl free radical (•OH), superoxide anion (O2•−), and malondialdehyde in the liver tissue were detected. The expression of Keap1, Nrf2, HO-1, and NQO1 were explored by Western blotting, and also the change of Nrf2 and keap1 was assessed by immunofluorescence. ResultsCompared with sham group, pathologic damage of graft-livers was in a time-dependent manner, accompanied with the increased level of oxidative stress in the AOLT group, and nuclear Nrf2 expression and its downstream antioxidant enzyme, HO-1 and NQO1, were also increased in this group. However, in propofol pretreatment groups especially in the high-dose group, the pathologic score was significantly decreased, accompanied with a lower level of •OH, O2•−, and malondialdehyde than that of the AOLT group. The change of oxidative stress might be related to the Nrf2 pathway, evidenced as the elevation of protein expression level of NQO1, HO-1, and nuclear Nrf2. ConclusionsProtective effects of propofol against liver transplantation–induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.

Can low dose of propofol effectively suppress fentanyl-induced cough during induction of anaesthesia? A double blind randomized controlled trial.

Background and Aims:Fentanyl-induced cough (FIC) is often seen after intravenous (IV) administration of fentanyl during the induction of general anesthesia. The aim of this study was to evaluate the effectiveness of low dose of propofol in suppressing of FIC during induction of anesthesia.Material and Methods:In a prospective double-blind randomized controlled trial, a total of 240 patients, American Society of Anesthesiologists physical status Class I and II, scheduled for elective surgery were randomly assigned into two equally sized groups (n = 120). Patients in Group A received low dose of propofol (10 mg) and patients in Group B received the same volume of normal saline (control group). Two minutes later, all patients were given fentanyl (2 μg/kg) over 2 s through the peripheral IV line in the forearm. The vital sign profiles and frequency and intensity of cough were recorded within 2 min after fentanyl bolus by a nurse blinded to study design. Data were analyzed using independent t-test, paired t-test and Chi-square test.Results:The incidences of FIC were 9.2% and 40.8% in Group A (propofol) and Group B (placebo) respectively (P = 0.04). Furthermore, there was a significant difference in the intensity of cough between Groups A and B (P < 0.0001). The hemodynamic value (systolic blood pressure, diastolic blood pressure, heart rate, mean arterial pressure and saturation of oxygen) were similar, and there was no significant difference between two groups in the baseline value or after propofol or placebo injection.

A Pilot Study of Cerebral and Hemodynamic Changes During Sedation with Low Dose of Thiopental Sodium or Propofol in Patients with Acute Brain Injury.

One of the most important therapeutic maneuvers in head injury patients is to maintain Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) within normal levels. To compare the effects of low dose of thiopental sodium and propofol on reducing ICP and CPP in patients with head injury that scheduled for neurosurgical interventions. Using a randomized, crossover pilot study, we enrolled patients with head injury that scheduled for neurosurgical interventions admitted to ICU unit of a teaching hospital during 2010 to 2011. In this pilot study, patients randomized into two equal groups. The first group received bolus injection of thiopental sodium 2 mg/kg and a maintenance dose of 2 mg/kg/h and the second group was given a bolus dose of propofol 0.5 mg/kg followed by propofol infusion 20 μg/kg/min. All of patients were given dexamethasone 8 mg at time of catheter insertion. ICP measurement catheter was inserted for each patient and ICP, CPP, SPO2 and MAP were recorded hourly for a period of 6 hours. There was no significant difference in sex and age between the two study groups (p>0.05). The mean ICP, CPP, SPO2 and arterial blood pressure were found to be similar with no significant difference between both groups (p>0.05). Both propofol and thiopental sodium were equally effective in monitoring and maintaining CPP and MAP and eventually an ideal SPO2.

Is acute severe asthma a risk factor for the propofol infusion syndrome?

Propofol infusion syndrome (PRIS) is a rare but potentially fatal syndrome observed more commonly in young obese men receiving high dose (usually >4mg/kg/hr) or long term (>48 hrs) propofol. It can cause metabolic acidosis, renal failure, rhabdomyolysis, hyperkalemia, and cardiac failure. We report a case of possible PRIS in a 24-year-old obese Hispanic man admitted for acute severe asthma who developed PRIS in less than 12 hours on lower doses of propofol (3 mg/kg/hr tapered within 3 hrs) while on concurrent corticosteroids. Patients with acute asthma and subclinical myopathy may be at increased risk for propofol toxicity and need careful monitoring if this drug is used for sedation.

Hepatotoxicity after Sevoflurane Exposure in a Patient with Chronic Hepatitis C: A Case Report

Sevoflurane is considered a safe inhaled anesthetic of choice in patients with liver disease. Compared to other halogenated inhaled anesthetics, Sevoflurane is reported to lessen the severity of decreased hepatic blood flow and undergoes a different mechanism of hepatic metabolism. In patients with preexisting liver disease, there is potential for low-flow Sevoflurane to induce acute liver damage through other mechanisms. Limited data exists to guide clinical decision-making when quantifying the severity of cirrhosis in patients with hepatitis C and its relationship to anesthesia choice. Previous studies have found that exposure to general anesthesia during abdominal surgery may increase the risk of hepatorenal failure. This study has raised a concern that anesthetics may interfere with various hepatic functions secondary to viral infection. The generation of abnormal liver enzymes and hypercoagulation has provided further exploration for such toxicity. A 53-year-old African American man, with a significant past medical history of controlled hypertension and chronic, uncontrolled Hepatitis C infection, and abdominal trauma in 1983, presented to the community hospital with abdominal discomfort with a 10 x 8 cm ventral hernia. The patient had an underlying hepatitis C infection, but was asymptomatic upon interview. Patient was subsequently scheduled for elective hernia repair for lysis of adhesions, component separation, and mesh placement. General anesthesia, which included low doses of fentanyl, propofol, rocuronium, and ketamine were maintained with sevoflurane, all of which lasted 4 hours. The patient remained hemodynamically stable throughout the procedure. Postoperatively, he showed signs of hemodynamic instability, suggestive of DIC and acute renal failure. Patient expired soon after, and autopsy revealed macronodular cirrhosis with dilated venous collaterals, pulmonary edema, and cardiomyopathy. This report demonstrates a clinical impact and further evaluation in current patient management. It creates awareness and demonstrates the necessity to evaluate patients with any severe disease and its contraindications to proposed treatment plans. Knowledge of anesthetic induced toxicities and comorbidities has been illustrated, as in the case with sevoflurane and chronic Hepatitis C. Although more studies are needed, physicians should determine the risks and benefits in such patients into operative procedures, as well as management strategies to prevent any possible mortality.

Anti-inflammatory effects of propofol during cardiopulmonary bypass: a pilot study.

Introduction:Propofol has been suggested as a useful adjunct to cardiopulmonary bypass (CPB) because of its potential protective effect on the heart mediated by a decrease in ischemia-reperfusion injury and inflammation at clinically relevant concentrations. In view of these potentially protective properties, which modulate many of the deleterious mechanism of inflammation attributable to reperfusion injury and CPB, we sought to determine whether starting a low dose of propofol infusion at the beginning of CPB would decrease inflammation as measured by pro-inflammatory markers.Materials and Methods:We enrolled 24 patients undergoing elective coronary artery bypass graft (CABG). The study group received propofol at rate of 120 mcg/kg/min immediately after starting CPB and was maintained throughout the surgery and for the following 6 hours in the intensive care unit (ICU). The control group received propofol dose of 30-50 mcg/kg/min which was started at the time of chest closure with wires and continued for the next 6 hours in the ICU. Interleukins (IL) -6, -8 and -10 and tumor necrosis factor alpha (TNFalpha) were assayed.Result:The most significant difference was in the level of IL-6 which had a P value of less than 0.06. Starting a low dose propofol early during the CPB was not associated with significant hemodynamic instability in comparison with the control group.Conclusion:Our study shows that propofol may be suitable as an anti-inflammatory adjunct for patients undergoing CABG.

Influence of intravenous anesthetics on neuromonitoring of the recurrent laryngeal nerve during thyroid surgery

Limited reports are available in the literature on the impact of intravenous administration of anesthetics on laryngeal electromyographic (EMG) activity. The purpose of this study was to determine the influence of the two commonly used intravenous anesthetics (propofol and thiamylal) on EMG amplitude evoked from the recurrent laryngeal nerve (RLN) during thyroid surgery. A total of 40 patients were randomized to receive a bolus of propofol (0.5 mg/kg; n = 20) or thiamylal (1.5 mg/kg; n = 20) to increase anesthetic depth when the surgeon found patient movement intraoperatively. Evoked potentials were obtained before and every 1 minute after the administration of each agent for up to 5 minutes by stimulating the RLN. The magnitude of evoked potentials at each time point and hemodynamic response were compared within groups. The mean amplitude of evoked potentials did not change significantly after administration of either propofol or thiamylal (p > 0.05 within groups). Mean arterial pressure measured from 1 minute to 5 minutes was significantly lower in the propofol group than in the thiamylal group (p < 0.05). Heart rate measured within 5 minutes did not differ significantly within groups. Low dose of propofol (0.5 mg/kg) or thiamylal (1.5 mg/kg) did not affect EMG readings during neuromonitoring of the RLN in thyroid surgery. Our results show that thiamylal provides better hemodynamic stability than propofol, and is therefore a preferable agent to increase anesthesia depth and prevent further patient movement during intraoperative neuromonitoring.

ABSTRACT 343

Background and aims: Propofol is an effective agent to provide sedation for children undergoing diagnostic imaging. Most regimens use propofol with a bolus induction dose followed by continuous infusion. We report the effectiveness of an intermittent bolus regimen for children undergoing MRI on an ambulatory basis. Aims: To establish the safety and efficacy of an intermittent low dose propofol regimen for children undergoing MRI. Methods: A retrospective chart review identified children who received this regimen from 2009–2012. The protocol includes comprehensive evaluation by a pediatric intensivist, premedication with midazolam 0.1 mg/kg, induction with propofol 1.5–2 mg/kg, followed by intermittent boluses of 1–1.5 mg/kg titrated to need. We report the induction time, sedation time, time to discharge, adverse events, need for additional agents, and failed sedation. Results: Data included 183 children, four were infants. Mean age was 4.8 years (SD 3.2), and body weight was 18.3 kg (SD 10). The mean induction dose was 2.1mg/kg (SD 0.5). The median induction time was 4 minutes (range 1–7 min.), sedation time 26 minutes (range 8–60), and time to discharge 14 minutes (range 5–45). Mean total dose of propofol was 2.7mg/kg (SD 1.1). 93 children (50.5%) completed the study with a single induction dose, while 15 (8.2%) required more than two doses. Sedation with a second agent was needed in 9 children (4.9%). Eight children (4.3%) needed airway manoeuvres and 27 (14.8%) experienced significant bradycardia. Three (1.6%) failed sedation. Conclusions: Intermittent dosing regimen of propofol was effective and well tolerated with mild events, but rarely some children failed or needed a second agent.

Effects of different doses of propofol on traumatic brain injury in rats

Objective To evaluate the effects of different doses of propofol on traumatic brain injury in rats .Methods Forty-eight healthy male Sprague-Dawley rats , aged 7-8 weeks , weighing 270-320 g , were randomly divided into 6 groups （ n=8 each ） using a random number table ：sham operation group （group S ） , traumatic brain injury group （group I） ,fat emulsion group （group F） and low-dose propofol group （group L） , medium-dose propofol group （group M ） ,and high-dose propofol group （group H ） .Traumatic brain injury model was established according to the method described by Feeney .In group S ,0.9% normal saline was infused into the left femoral vein at 3.49 ml·kg-1 ·h-1 .In I ,F ,L ,M and H groups ,0.9% normal saline ,20% fat emulsion 3.49 ml·kg-1 ·h-1 ,and propofol 17.46 ,34.92 and 69.84 mg·kg-1 ·h-1 were infused into the left femoral vein ,respectively .Blood samples were collected from the right common carotid artery at 15 and 60 min of infusion （T1-2 ） for determination of serum S100β protein concentrations . The rats were then sacrificed after collecting blood samples at T2 and brains were removed for microscopic examination of the pathological changes of the cerebral cortex （light microscope ） and ultrastructure of neurons in the cerebral cortex （transmission electron microscope） .Results The serum S100β protein concentrations were significantly higher at T1 ,2 in the other five groups than in group S （ P〈0.05 ） .Compared with I and F groups ,the serum S100βprotein concentrations were＆nbsp;significantly decreased at T1 ,2 in L ,M and H groups （ P〈0.05） .Compared with group L ,the serum S100βprotein concentrations were significantly decreased at T2 in M and H groups , and the serum S100β protein concentrations were increased at T1 in H group （ P〈 0.05 ） . The serum S100β protein concentrations were significantly higher at T1 ,2 in H group than in group M （ P〈0.05 ） .Light microscopic examination showed that nucleus condensation , cell necrosis , and cell edema were significantly attenuated in L ,M , and H groups as compared with group I;normal neurons could be found in group M .Transmission electron microscopic examination showed that the severity of neuronal damage was significantly attenuated in L ,M ,and H groups as compared with group I .Conclusion Different doses of propofol can reduce traumatic brain injury in rats . Key words: Propofol; Brain injuries

Influence of valproate on the required dose of propofol for anesthesia during electroconvulsive therapy of bipolar affective disorder patients

BackgroundPropofol is often used as an anesthetic agent for electroconvulsive therapy (ECT). In recent studies, propofol was shown to possess significant seizure-shortening properties during ECT. “Valproate” is a mood stabilizer used mainly in the treatment of bipolar affective disorder. It is reported that valproate, being an anticonvulsant, raises the seizure threshold, thus decreases the efficacy of ECT treatment.AimThe purpose of our study was to compare the dose of propofol in valproate-using patients and valproate-free patients.MethodsIn an open design, 17 patients with bipolar affective disorder manic episodes who were to be treated with valproate and ECT in combination, were compared with 16 manic-episode patients who were to be treated with ECT but not valproate. The two groups were compared on the basis of electroencephalography-registered seizure duration and the propofol dosage required to induce anesthesia.ResultsValproate, compared with no valproate treatment, results in a decrease in the propofol dose required to induce anesthesia. In the valproate group of study participants, seizure duration was significantly shorter than in the valproate-free group.ConclusionThe results suggest that valproate reduces the dose of propofol required for anesthesia during ECT treatment in patients with bipolar affective disorder manic episodes. Although propofol is a safe and efficacious anesthetic for ECT treatment, lower doses of propofol should be used to induce anesthesia for patients under valproate treatment. When the clinician needs to prolong seizure duration in patients treated with valproate, interruption of the valproate treatment or an anesthetic agent other than propofol should be considered.

Electroconvulsive therapy pre-treatment with low dose propofol: Comparison with unmodified treatment

BackgroundWhilst electroconvulsive therapy (ECT) is routinely administered under anesthesia in developed nations, in many developing countries, ECT is still administered unmodified. This practice has attracted considerable scrutiny with calls to ban unmodified ECT. However, there are no affordable alternatives for many poor, acutely ill psychiatric patients. We evaluated whether administration of intravenous propofol 0.5 mg/kg for sedation by the ECT psychiatrist just prior to otherwise unmodified treatment improved acceptance of and reduced anxiety surrounding the treatment. MethodWe conducted an open label trial at The King George's Medical University in Lucknow, India. Forty-nine patients received propofol pre-treatment and 50 patients received unmodified treatment as usual. ResultsSocio-demographic profiles, diagnoses and clinical responses were comparable. Patients who received propofol experienced less anxiety monitored by the State-Trait Anxiety Inventory just prior to ECT (p < 0.001), and had a more favorable attitude towards treatment assessed by an established questionnaire (Freeman and Kendell, 1980). Propofol patients were less likely to experience post-ictal delirium monitored by the CAM-ICU (p = 0.015) and had fewer cognitive side-effects on the MMSE (p = 0.004). There were no adverse events associated with propofol administration. ConclusionWhilst unmodified ECT should never be used when modified ECT under anesthesia is available, we have found low dose propofol can be safely administered by the ECT psychiatrist to sedate patients pre-treatment who would otherwise receive completely unmodified treatment. The intervention was associated with reduced anxiety and a more positive attitude towards ECT, without compromising efficacy. A randomized double blind controlled study is necessary to confirm these benefits.

The Effect of Propofol on Intrathecal Morphine-Induced Pruritus and Its Mechanism

Previous studies have shown that a low dose of propofol IV bolus had a beneficial effect on intrathecal morphine-induced pruritus in humans. However, its exact mechanism has not been fully understood. In this study, we hypothesized that propofol relieved intrathecal morphine-induced pruritus in rats by upregulating the expression of cannabinoid-1 (CB[1]) receptors in anterior cingulate cortex (ACC). Twenty-four Sprague-Dawley rats were divided into a control group and 20, 40, 80 μg/kg morphine groups to create an intrathecal morphine-induced scratching model. The effects of propofol on intrathecal 40 μg/kg morphine-induced scratching responses were then evaluated. Sixty rats were randomly assigned to control, normal saline, intralipid, and propofol groups, with pruritus behavior observation or killed 8 minutes after venous injection of normal saline, intralipid, or propofol, and brain tissues were then collected for assay. Immunohistochemistry was then performed to identify the expression of CB (1) receptor in ACC, and the concentration of CB(1) receptor in ACC was determined by Western blot analysis. Compared with the control group, rats in the 20, 40, 80 μg/kg morphine groups had higher mean scratching response rates after intrathecal morphine injection (P =0.020, 0.005, and 0.002, respectively). There was a statistical difference between 20 and 40 μg/kg morphine groups at 10 to 15 and 15 to 20 timepoints after intrathecal morphine injection (P = 0.049 and 0.017, respectively). Propofol almost abolished the scratching response that was induced by 40 μg/kg intrathecal morphine injection (F[2, 15] = 46.87, P < 0.001; F[22, 165] = 2.37, P = 0.001). Compared with the intralipid and normal saline groups, the scratching behavior was significantly attenuated in the propofol group (P < 0.001). Compared with control, normal saline, and intralipid groups, the protein expression of CB(1) receptor in ACC (Western blot) in the propofol group increased (0.86 ± 0.21, 0.94 ± 0.18, 0.86 ± 0.13, and 1.34 ± 0.32, respectively, P < 0.001). There was no significant difference among control, normal saline, and intralipid groups. Compared with the control, normal saline, and intralipid groups, the average number of neurons of CB(1) receptor in the ACC area were higher in the propofol group (21.0 ± 1.4, 19.3 ± 1.8, 24.8 ± 7.7, and 37.2 ± 3.3, respectively, P < 0.001). Morphine elicits dose-independent scratching responses after intrathecal injection in rats. Morphine 40 μg/kg intrathecal injection-induced scratching responses can be prevented by propofol. Increased protein expression of CB(1) receptors in ACC may contribute to the reversal of intrathecal morphine-induced scratching.

Propofol Impairs Neurogenesis and Neurologic Recovery and Increases Mortality Rate in Adult Rats After Traumatic Brain Injury*

Limited data are available on the influence of sedation for critical care therapy with the widely used anesthetic propofol on recovery from acute traumatic brain injury. To establish the influence of propofol on endogenous neurogenesis and functional recovery after traumatic brain injury, rats were sedated with propofol either during or 2 hours after experimental traumatic brain injury. Randomized controlled animal study. University research laboratory. One hundred sixteen male Sprague Dawley rats. Mechanical brain lesion by controlled cortical impact. This study investigated the dose-dependent influence of propofol (36 or 72 mg/kg/hr) either during controlled cortical impact induction or in a delayed application protocol 2 hours after experimental traumatic brain injury. Infusion of propofol resulted in 1) aggravation of neurologic dysfunction, 2) increased 28-day mortality rate, and 3) impaired posttraumatic neurogenesis (5-bromo-2-deoxyuridine + NeuN-positive cells). Application of propofol during trauma induction afforded a significant stronger effect in the high-dose group compared with low-dose propofol. In the posttrauma protocol, animals were sedated with sevoflurane during the controlled cortical impact injury, and propofol was given after an awake phase. In these animals, propofol increased mortality rate and impaired neurologic function and neurogenesis compared with animals without delayed propofol anesthesia. The results show that propofol may prevent or limit reparative processes in the early-phase postinjury. The results therefore indicate that anesthetics may be potentially harmful not only in very young mammalians but also in adult animals following acute cerebral injuries. The results provide first evidence for an altered sensitivity for anesthesia-related negative effects on neurogenesis, functional outcome, and survival in adult rats with brain lesions.

Prediction Variability of Combined Pharmacokinetic Pharmacodynamic Models: A Simulation Study of Propofol in Combination with Remifentanil and Fentanyl

Introduction: The aims of this study were to estimate model prediction variability for drug concentrations and effects during a simulated propofol-remifentanil-fentanyl anesthetic and identify the change in propofol infusion rates or fentanyl bolus doses necessary to detect changes in the duration of selected drug effects. We hypothesized that drug effect variability is large when drug concentrations are within the dynamic range of concentration effect curves (i.e. during emergence from anesthesia), but when drug concentrations are above or below the dynamic range variability is small. Methods: 1000 parameter sets were randomly generated from published pharmacokinetic model parameters and their metrics of variability and published pharmacodynamic remifentanil-propofol interaction model parameters and their metrics of variability for loss of response to laryngoscopy, loss of responsiveness, analgesia, and intolerable ventilatory depression. 1000 simulated patients were administered 90-minute combined remifentanil (0.20 mcg/kg/ min) and propofol (100 mcg/kg/min) infusions, and two fentanyl boluses at 0 and 75 minutes of 2 mcg/kg. Results: The drug effect site concentration variability was larger for remifentanil than for propofol. The drug effect variability was minimal during the anesthetic but large during emergence. Moderate changes in infusion rates and bolus sizes caused minimal changes in the duration of drug effect following termination of the anesthetic. Conclusion: Simulations in part confirmed our hypotheses; during the anesthetic, despite considerable concentration variability, drug effect variability is small at points of clinical interest. The combined low dose propofol and high dose remifentanil infusions provide a high probability of unresponsiveness and analgesia throughout the anesthetic. During emergence, however, drug effect variability is large and substantial dose changes are required to detect a difference in duration of selected effects.