thiopental and Obesity

The prevalence of obesity has increased 15% up to 20% and represents an important challenge for the anesthesiologist in drug-dosing management. The aim of this work is to provide an overview on physiological changes and pharmacokinetic implications of obesity for the anesthesiologist. Obesity increases both fat and lean masses; however, the percentage of fat tissue increases more than does the lean mass, affecting the apparent volume of distribution of anesthetic drugs according to their lipid solubility. Benzodiazepine loading doses should be adjusted on actual weight, and maintenance doses should be adjusted on ideal body weight. Thiopental sodium and propofol dosages are calculated on total body weight (TBW). The loading dose of lipophilic opioids is based on TBW, whereas maintenance dosages should be cautiously reduced because of the higher sensitivity of the obese patient to their depressant effects. Pharmacokinetic parameters of muscle relaxants are minimally affected by obesity, and their dosage is based on ideal rather than TBW. Inhalation anesthetics with very low lipid solubility, such as sevoflurane and desflurane, allow for quick modification of the anesthetic plan during surgery and rapid emergence at the end of surgery, hence representing very flexible anesthetic drugs for use in this patient population. Drug dosing is generally based on the volume of distribution for the loading dose and on the clearance for maintenance. In the obese patient, the volume of distribution is increased if the drug is distributed both in lean and fat tissues whereas the anesthetic drug clearance is usually normal or increased.

Topics: Analgesics, Opioid; Anesthetics; Benzodiazepines; Cardiovascular Physiological Phenomena; Humans; Muscle Relaxants, Central; Obesity; Propofol; Respiratory Physiological Phenomena; Thiopental

To determine the effects of induction agent and obesity on the change in functional residual capacity caused by induction of anaesthesia, we measured the change in end-expiratory respiratory volume (EERV) during induction of anaesthesia with either thiopentone or propofol. Female patients breathed via a face mask from a closed circle system connected to a water spirometer. The spirometer tracing was used to measure the decrease in EERV. The median decrease was 200 (95% confidence limits 90-280) ml after thiopentone and 285 (200-425) ml after propofol. The decrease in each group was significant (P < 0.01) but there was no difference between the two groups. The change in EERV, expressed as a proportion of the predicted functional residual capacity, was not related to obesity (estimated as the ratio of actual to predicted body weight).

Topics: Adult; Anesthesia, General; Female; Functional Residual Capacity; Humans; Masks; Obesity; Propofol; Residual Volume; Thiopental; Time Factors

Topics: Adult; Aged; Anesthesia, Conduction; Anesthesia, General; Anesthesia, Spinal; Carbon Dioxide; Cardiac Output; Female; Halothane; Humans; Hypotension; Lidocaine; Middle Aged; Obesity; Oxygen; Pulmonary Atelectasis; Thiopental

This work evaluates solid lipid nanoparticles of thiopental sodium against obesity-induced cardiac dysfunction and hypertrophy and explores the possible mechanism of action. TS loaded SLNs were formulated by hot-homogenization and solvent diffusion method. TS-SLNs were scrutinized for entrapment efficiency, drug loading capacity, gastric stability, particle size, in vitro drug release. Mice were feed with the normal chow or high-fat diet for 08 weeks to induce obesity and primary cardiomyocytes. The therapeutic effects of thiopental sodium in the high fat diet (HFD) induced cardiac hypertrophy. Systolic blood pressure (SBP) was estimated at a regular time interval. At the end of the experimental study, systolic pressure left ventricular, LV end-diastolic pressure and rate of increase of LV pressure and antioxidant, apoptosis, cytokines and inflammatory scrutinized. HFD induced group mice exhibited a reduction in the body weight and enhancement of cardiac hypertrophy marker and dose-dependent treatment of thiopental sodium up-regulation the body weight and down-regulated the cardiac hypertrophy. Thiopental sodium significantly (

Topics: Animals; Antioxidants; Apoptosis; Blood Pressure; Cardiomegaly; Chemistry, Pharmaceutical; Diet, High-Fat; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Liberation; GABA Modulators; Heart Diseases; Inflammation; Inflammation Mediators; Lipids; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Nanoparticles; Obesity; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Particle Size; Thiopental; Weight Loss

The increased use of phytotherapeutic drugs means that anesthetists are more often confronted with these drugs. In this case report possible problems which can occur are demonstrated exemplified by silexan. Silexan is a phytotherapeutic anxiolytic which is used in anxiety disorders. Because of its potential mechanism of action via the neurotransmitter gamma-aminobutyric acid (GABA) receptors interactions with narcotic drugs are possible. The case of an 18-year-old girl who underwent an operation under general anesthesia while taking silexan as long-term medication is presented. The desired depth of narcosis could only be reached by inhalative induction with sevoflurane after unsuccessful induction attempts using intravenous propofol and thiopental. Possible explanations for this route and inhalative induction as a possible alternative are discussed.

Topics: Adolescent; Anesthesia, Intravenous; Anesthetics; Anesthetics, Intravenous; Arachnoid Cysts; Cerebellar Diseases; Drug Interactions; Female; GABA Antagonists; Humans; Hypnotics and Sedatives; Injections, Intravenous; Lavandula; Neurosurgical Procedures; Obesity; Oils, Volatile; Plant Oils; Postoperative Nausea and Vomiting; Propofol; Receptors, GABA-A; Thiopental

The effect of obesity on the shape of drug disposition curves was explained using the residence time concept without assuming well-mixed compartments. The mean (MDRT) and relative dispersion (RD2(D)) of disposition residence time of drug were predicted as function of percentage body fat by lumping the organs into fat and nonfat tissues, utilizing the fact that MDRT and RD2(D) act as a scale and shape parameter of disposition curves, respectively. The longer sojourn time of lipophilic drugs in adipose tissue leads to an increase in RD2(D) when the fraction of body fat increases. This explains the change in the shape of disposition curves observed in obese patients, where the increase in MDRT is accompanied by a proportionately great prolongation of the terminal half life. The model also predicts a decrease in whole body distribution clearance with increasing residence time dispersion (RD2(D)).

Topics: Adiposity; Animals; Dogs; Half-Life; Humans; Hypnotics and Sedatives; Models, Statistical; Obesity; Pharmacokinetics; Rats; Thiopental; Tissue Distribution

To investigate the relationship between total body weight (TBW) or body mass index (BMI) and atracurium reversal time.. The study population comprised 25 patients with TBW < 80 kg and 25 patients with TBW > or = 80 kg anaesthetised with midazolam, thiopentone, fentanyl, nitrous oxide and halothane. Neuromuscular block was induced with 0.5 mg.kg-1 atracurium and maintained with doses of 0.15 mg.kg-1. Neuromuscular transmission was recorded using train-of-four (TOF) nerve stimulation and mechanomyography. Neostigmine, 0.07 mg.kg-1, was administered when the first twitch in TOF had recovered to 10% of control. Reversal time was defined as: time from administration of neostigmine until TOF ratio recovered to 0.70.. There was no difference in reversal time between patients with TBW < 80 kg (7.2 +/- 2.6 min, mean +/- SD), and patients with TBW > or = 80 kg (6.9 +/- 3.6 min). When patients were grouped according to BMI there was no difference in reversal time between groups with low BMI (6.9 +/- 2.6 min) or high BMI (7.1 +/- 3.6 min). There was, furthermore, no difference in reversal time between the 15 patients in the study population with the smallest TBW or BMI and the 15 patients with the greatest TBW or BMI. There was no correlation between TBW or BMI and reversal time.. When atracurium-induced neuromuscular block is antagonised with 0.07 mg.kg-1 neostigmine. TBW or BMI have no influence on reversal time.

Topics: Adult; Anesthetics, Inhalation; Anesthetics, Intravenous; Atracurium; Body Mass Index; Body Weight; Cholinesterase Inhibitors; Electric Stimulation; Female; Fentanyl; Halothane; Humans; Midazolam; Middle Aged; Muscle Contraction; Muscle, Skeletal; Neostigmine; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Nitrous Oxide; Obesity; Synaptic Transmission; Thiopental; Time Factors; Ulnar Nerve

We report a case of ischaemic optic neuropathy which occurred after prolonged spine surgery in the prone position in an obese, diabetic patient.. The patient was a 44-yr-old, 123 kg, 183 cm man for decompressive laminectomy and instrumented fusion of the lumbar spine. Anaesthesia was induced with thiopentone, fentanyl and succinylcholine and maintained with nitrous oxide, oxygen, isoflurane and a fentanyl infusion. He was positioned prone on the Relton-Hall frame and had an uneventful intraoperative course. Estimated blood loss was 3,000 ml. He was taken to the surgical intensive care unit (SICU) and the trachea was extubated 3.5 hr later. He had no pulmonary or haemodynamic problems and went to a regular nursing floor in the morning. He was discharged home on postoperative day #5. He telephoned his surgeon on postoperative day #7 to say that his vision had been blurry since surgery. His visual acuity was decreased, and on examination, he had a bilateral papillary defect, optic swelling and a splinter haemorrhage in the right eye. Magnetic resonance imaging (MRI) scan of the head and orbits detected no other abnormality. Based on this examination, he was felt to have bilateral ischaemic optic neuropathy and treated conservatively. By postoperative day #47, his visual acuity was greatly improved and near normal. Careful review of possible contributing factors suggests that the cause of the ischaemic optic neuropathy was venous engorgement.. This patient developed ischaemic optic neuropathy from a prolonged interval in the prone position of the Relton-Hall frame, which may be related to venous engorgement.

Topics: Adult; Anesthesia, Intravenous; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Loss, Surgical; Diabetes Mellitus, Type 1; Fentanyl; Hemorrhage; Humans; Immobilization; Isoflurane; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Neuromuscular Depolarizing Agents; Nitrous Oxide; Obesity; Optic Nerve; Optic Neuropathy, Ischemic; Oxygen; Papilledema; Prone Position; Spinal Fusion; Spinal Stenosis; Succinylcholine; Thiopental; Time Factors; Vascular Diseases; Veins; Visual Acuity

Verification of the proper placement of a tracheal tube by capnography in rapid sequence induction can lead to aspiration if the patient is ventilated with the tube in the esophagus. In this study we have associated the capnography with the esophageal detector device as modified by Nunn. In 49 patients, two endotracheal tubes were introduced, one in the esophagus and the other in the trachea. An anesthesiologist, unaware of which tube is in the trachea, squeezed the bulb of the esophageal detector device, attached it to the sidestream of the capnography and the endotracheal tubes, then released it. No reinflation of the bulb was seen with the esophageal tube. Two types of reinflation were seen with the tracheal tube: slow (6 cases), all were obese, and instant (43 cases) in the remaining patients. The air aspirated from the respiratory tract by the bulb was analyzed by the capnograph; CO2 was detected from all the tracheal tubes but not from the esophageal ones. We concluded that the esophageal detector device and capnography used as described in our study is a simple reliable test to confirm the proper placement of a tracheal tube before starting ventilation in rapid sequence induction.

Topics: Adolescent; Adult; Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Capnography; Carbon Dioxide; Equipment Design; Esophagus; Female; Fentanyl; Humans; Intubation, Intratracheal; Male; Middle Aged; Obesity; Reproducibility of Results; Respiration, Artificial; Single-Blind Method; Suction; Thiopental

Understanding the influence of physiological variables on thiopental pharmacokinetics would enhance the scientific basis for the clinical usage of this anesthetic.. A physiological pharmacokinetic model for thiopental previously developed in rats was scaled to humans by substituting human values for tissue blood flows, tissue masses, and elimination clearance in place of respective rat values. The model was validated with published serum concentration data from 64 subjects. The model was simulated after intravenous thiopental administration, 250 mg, over 1 min, to predict arterial plasma concentrations under conditions of different cardiac outputs, degrees of obesity, gender, or age.. The human pharmacokinetic model is characterized by a steady state volume of distribution of 2.2 l/kg, an elimination clearance of 0.22 l/min, and a terminal half-life of 9 h. Measured thiopental concentrations are predicted with an accuracy of 6 +/- 37% (SD). Greater peak arterial concentrations are predicted in subjects with a low versus a high cardiac output (3.1 and 9.4 l/min), and in subjects who are lean versus obese (56 and 135 kg). Acutely, obesity influences concentrations because it affects cardiac output. Prolonged changes are due to differences in fat mass. Changes with gender and age are relatively minor.. The physiological pharmacokinetic model developed in rats predicts thiopental pharmacokinetics in humans. Differences in basal cardiac output may explain much of the variability in early thiopental disposition between subjects.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anesthetics, Intravenous; Animals; Body Composition; Cardiac Output; Computer Simulation; Female; Humans; Male; Middle Aged; Models, Biological; Obesity; Rats; Regional Blood Flow; Sex Factors; Thiopental

Obese patients have a decreased functional residual capacity and, hence, a reduced oxygen supply during periods of apnea. To determine whether obese patients are at greater risk of developing hypoxemia during induction of anesthesia than patients of normal weight, 24 patients undergoing elective surgical procedures were studied. Group 1 (normal) were within 20% of their ideal body weight. Group 2 (obese) were more than 20% but less than 45.5 kg over ideal body weight. Group 3 (morbidly obese) were more than 45.5 kg over ideal body weight. Patients were preoxygenated for 5 min or until expired nitrogen was less than 5%. After induction of anesthesia and muscle relaxation the patients were allowed to remain apneic until arterial saturation as measured by pulse oximetry reached 90%. The time taken for oxygen saturation to decrease to 90% was 364 +/- 24 s in group 1, 247 +/- 21 s in group 2, and 163 +/- 15 s in group 3; these times are significantly different at P less than 0.05 between groups. Regression analysis of the data demonstrated a significant negative linear correlation (r = -0.83) between time to desaturation and increasing obesity. These results show that obese patients are at an increased risk of developing hypoxemia when apneic.

Topics: Adult; Anesthesia; Apnea; Humans; Hypoxia; Middle Aged; Obesity; Obesity, Morbid; Risk; Thiopental

The cranio-caudal movement of the sternum was studied by the technique of video magnification during induction of anaesthesia with thiopentone 2-4 mg kg-1 i.v. in 20 patients. Anaesthesia produced no consistent change in end-expiratory position of the sternum; there was a range of movement from 3.1 mm cephalad to 5.4 mm caudad. There was a significant relationship between movement and degree of obesity of the patient (P less than 0.01), with the sternum tending to caudal movement in the obese patient.

Topics: Anesthesia, Intravenous; Female; Humans; Movement; Obesity; Respiration; Sternum; Thiopental; Video Recording

The effect of obesity on the disposition kinetics of thiopental was studied in seven morbidly obese (age 25 to 46 years) and eight age-matched lean patients (age 25 to 43 years), undergoing primarily abdominal surgery. Based upon total (bound + free) thiopental concentrations, the average (+/-SD) volumes of distribution in the terminal disposition phase and at steady-state (V beta and V ss) were significantly larger in the obese (7.94 +/- 4.55 1/kg and 4.72 +/- 2.73 1/kg, respectively) than in the age-matched lean patients (1.95 +/- 0.63 1/kg and 1.40 +/- 0.46 1/kg, respectively). Clearance of total thiopental, normalized for total body weight was not significantly different between the obese (0.18 +/- 0.081 . h-1 . kg-1) and lean patients (0.21 +/- 0.06 1 . h-1 . kg-1). However, total body clearance not normalized for total body weight was significantly larger in the obese (24.98+/- 14.87 1/h) than in the lean patients (11.86 +/- 3.66 1/h). The elimination half-life of thiopental was significantly longer in the obese (27.85 h) than in the lean patients (6.33 h) and this difference was primarily a function of a larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (range, 17.8 per cent to 27.6 per cent) was not correlated with the degree of obesity. The most appropriate means of comparing intrinsic metabolizing capacity (i.e., normalized vs. non-normalized for weight) between lean and obese subjects remains unresolved.

Topics: Abdomen; Adult; Blood Proteins; Female; Humans; Kinetics; Male; Middle Aged; Obesity; Protein Binding; Thiopental

Thiopental was administered for seizure control in 2 patients with uncontrollable seizures. Serum samples were collected from each patient and assayed for thiopental, and the resulting serum concentration--time data were analyzed pharmacokinetically. The biologic half-life in both patients was significantly longer than previously reported values. Based on the limited number of patients studied, it would appear that half-life and volume of distribution increase with the degree of obesity, while clearance remains unchanged. These pharmacokinetic characteristics would be worthy of consideration in cases where there may be prolonged use of thiopental, eg., for the control of uncontrollable seizures.

Topics: Adolescent; Adult; Epilepsy, Post-Traumatic; Female; Half-Life; Humans; Kinetics; Obesity; Seizures; Thiopental

Sixteen extremely obese patients were anaesthetized for intestinal short circuiting operations. Severe obesity may cause pathological cardio-pulmonary changes. Cardiovascular alterations include increased systemic, pulmonary artery and pulmonary capillary venous pressure. Cardiac output, total blood volume and left ventricular work increase. Expiratory reserve volume and consequently functional residual capacity decrease with gross obesity. Functional residual capacity falls below closing volume and inspired gas may be distributed to non-dependent lung zones, resulting in decreased ventilation/perfusion ratios and arterial hypoxaemia. Low total respiratory compliance increases the oxygen cost of the work of breathing. Obesity may change the dose requirements for regional anaesthesia and long-acting muscle relaxants. General anaesthesia may also reduce functional residual capacity. We used a technique of anaesthesia which consisted of epidural analgesia with intra-operative mechanical ventilation and which specifically avoided volatile inhalation agents and long-acting muscle relaxants. All patients were extubated immediately after operation and returned to the recovery room for an average duration of 26 hours. Post-operative treatment included humidified oxygen, chest physiotherapy and elevation of the head of the bed to 45 degrees. Each patient's respiratory progress was monitored by repeated determinations of arterial blood gases and vital capacity and by serial chest X-rays. None of the patients in this group required post-operative tracheal intubation and mechanical ventilation.

Topics: Anesthesia, Epidural; Anesthesia, General; Epinephrine; Humans; Intestines; Intubation, Intratracheal; Length of Stay; Lidocaine; Lung Volume Measurements; Obesity; Postoperative Care; Respiration, Artificial; Succinylcholine; Thiopental; Vital Capacity

Topics: Anesthesia, Intravenous; Apnea; Carbon Dioxide; Humans; Hydrogen-Ion Concentration; Laryngoscopy; Larynx; Microsurgery; Obesity; Oxygen; Succinylcholine; Thiopental

Topics: Adolescent; Adult; Aged; Anesthesia, General; Apnea; Body Weight; Female; Halothane; Humans; Intubation; Intubation, Intratracheal; Larynx; Liver Function Tests; Male; Meperidine; Methoxyflurane; Middle Aged; Neuromuscular Depolarizing Agents; Nitrous Oxide; Obesity; Oxygen; Pharynx; Succinylcholine; Thiopental; Time Factors

Topics: Adolescent; Adult; Aged; Anesthesia, Inhalation; Blood Urea Nitrogen; Creatinine; Diuresis; Female; Humans; Kidney; Kidney Function Tests; Male; Methoxyflurane; Middle Aged; Obesity; Osmolar Concentration; Postoperative Complications; Sodium; Succinylcholine; Thiopental; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Anesthesia, General; Blood Pressure Determination; Body Height; Body Weight; Fentanyl; Halothane; Humans; Methoxyflurane; Nitrous Oxide; Obesity; Posture; Preanesthetic Medication; Thiopental; Time Factors

Topics: Adult; Anesthesia; Female; Humans; Meperidine; Mepivacaine; Methoxyflurane; Obesity; Pentobarbital; Succinylcholine; Thiopental

Topics: Acidosis; Apnea; Atropine; Bicarbonates; Bis-Trimethylammonium Compounds; Gallamine Triethiodide; Humans; Infusions, Parenteral; Laparotomy; Meperidine; Neostigmine; Nitrous Oxide; Obesity; Peritonitis; Postoperative Complications; Sodium Bicarbonate; Thiopental; Toxicology