Hendrikus J. M. Lemmens

Lean Body Weight Scalar for the Anesthetic Induction Dose of Propofol in Morbidly Obese Subjects

BACKGROUND: The unique anesthetic risks associated with the morbidly obese (MO) population have been documented. Pharmacologic management of these patients may be altered because of the physiologic and anthropometric changes associated with obesity. Unfortunately, studies examining the effects of extreme obesity on the pharmacology of anesthetics have been sparse. Although propofol is the induction drug most frequently used in these patients, the appropriate induction dosing scalar for propofol remains controversial in MO subjects. Therefore, we compared different weight-based scalars for dosing propofol for anesthetic induction in MO subjects. METHODS: Sixty MO subjects (body mass index ≥40 kg/m2) were randomized to receive a propofol infusion (100 mg · kg−1 · h−1) for induction of anesthesia based on total body weight (TBW) or lean body weight (LBW). Thirty control subjects (body mass index ⩽25 kg/m2) received a propofol infusion (100 mg · kg−1 · h−1) based on TBW. Syringe drop was used as the marker for loss of consciousness (LOC), at which point the propofol infusion was stopped. The propofol dose required for syringe drop and time to LOC were recorded. RESULTS: Total propofol dose (mg/kg) required for syringe drop and time to LOC were similar between control subjects and MO subjects given propofol based on LBW. MO subjects receiving a propofol infusion based on TBW had a significantly larger propofol dose and significantly shorter time to LOC. There was a strong relationship between LBW and total propofol dose received in all 3 groups. CONCLUSION: LBW is a more appropriate weight-based scalar for propofol infusion for induction of general anesthesia in MO subjects.

Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

BackgroundAcetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.MethodsPatients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events.ResultsEighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group.ConclusionsRecovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).

Regional anesthesia and obesity

Purpose of review Worldwide, the number of overweight and obese patients has increased dramatically. As a result, anesthesiologists routinely encounter obese patients daily in their clinical practice. The use of regional anesthesia is becoming increasingly popular for these patients. When appropriate, a regional anesthetic offers advantages and should be considered in the anesthetic management plan of obese patients. The following is a review of regional anesthesia in obesity, with special consideration of the unique challenges presented to the anesthesiologist by the obese patient. Recent findings Recent studies report difficulty in achieving peripheral and neuraxial blockade in obese patients. For example, there is an increased incidence of failed blocks in obese patients compared with similar, normal weight patients. Despite difficulties, regional anesthesia can be used successfully in obese patients, even in the ambulatory surgery setting. Summary Successful peripheral and neuraxial blockade in obese patients requires an anesthesiologist experienced in regional techniques, and one with the knowledge of the physiologic and pharmacologic differences that are unique to the obese patient.

Perioperative pharmacology in morbid obesity

Purpose of review Morbid obesity alters drug dose requirement and time course of drug response. In addition, morbid obesitys impact on many organ systems decreases the margin of safety of anesthetic drugs. Consequently, incorrect dosing will increase the rate of perioperative complications. In this review, we will discuss factors that affect the pharmacokinetics and pharmacodynamics of anesthetic agents in the obese population, we specify certain dosing scalars, and we relate our current knowledge of obesitys effects on the clinical pharmacology of anesthetic drugs. Recent findings A morbidly obese individuals increased cardiac output requires administration of higher drug doses than would be required for a standard-size person to attain the same peak-plasma concentration. Lean body weight (LBW) is highly correlated with the increased cardiac output, more so than fat mass or other variables. For most drugs, clearance increases nonlinearly with total body weight but linearly with LBW. Morbid obesity has no clinically significant impact on the uptake of the inhalation anesthetics isoflurane, sevoflurane, and desflurane when used in routine clinical practice. Total body weight dosing of neuromuscular blocking agents will result in a prolonged effect. Summary For the induction dose of hypnotics and the initial dose of other drugs that have a fast onset of effect, cardiac output or LBW are relevant dosing scalars. For maintenance dosing, LBW seems to be a more appropriate dosing scalar than total body weight.

Obesity Modestly Affects Inhaled Anesthetic Kinetics in Humans

BACKGOUND:Few studies have determined the effect of obesity on inhaled anesthetic pharmacokinetics. We hypothesized that the solubility of potent inhaled anesthetics in fat and increased body mass index (BMI) in obese patients interact to increase anesthetic uptake and decrease the rate at which the delivered (FD) and inspired (FI) concentrations of an inhaled anesthetic approach a constantly maintained alveolar concentration (end-tidal or FA). This hypothesis implies that the effect of obesity would be greater with a more soluble anesthetic such as isoflurane versus desflurane. METHODS:In 107 ASA physical status I–III patients, anesthesia was induced with propofol, tracheal intubation facilitated with neuromuscular blockade, and ventilation controlled with 50% nitrous oxide in oxygen to maintain end-tidal carbon dioxide concentrations between 35 and 45 mm Hg. Isoflurane or desflurane was administered in a 1 L/min inflow rate at FD concentrations sufficient to maintain FA at 0.6 minimum alveolar anesthetic concentration (0.7% or 3.7%, respectively). FD, FI, and FA were measured 5, 10, 20, 40, 60, 90, 120,150, and 180 min after starting potent inhaled anesthetic delivery. RESULTS:Fifty-nine patients received isoflurane and 48 received desflurane. BMI ranged between 18 and 63 kg/m2 and demographic variables did not differ between anesthetic groups. For isoflurane, FD/FA or FI/FA weakly (but significantly) correlated with BMI at 9/18 time points whereas for desflurane FD/FA or FI/FA correlated significantly with BMI at only one time point (P < 0.01). After dividing each group into nonobese (BMI < 30) and obese (BMI ≥ 30) patients, with isoflurane, FD/FA or FI/FA was higher in obese patients at four time points whereas there was no difference between nonobese and obese patients for desflurane. Patients receiving isoflurane took longer to respond to command after discontinuing anesthesia but obesity did not increase or decrease awakening time for either isoflurane or desflurane. When BMI was used to normalize FI/FA and FD/FA the median values for isoflurane consistently exceeded the median value for desflurane by factors ranging from 3 to 5, values comparable to the ratios of their blood/gas (3.1), muscle/gas (4.6), and fat/gas (5.4) partition coefficients. CONCLUSION:BMI modestly affects FD/FA and FI/FA, and this effect is most apparent for an anesthetic having a greater solubility in all tissues. An increased BMI increases anesthetic uptake and, thus, the need for delivered anesthetic to sustain a constant alveolar anesthetic concentration, particularly with a more soluble anesthetic. However, the increase with an increased body mass is small.

The Effect of Deliberate Hypercapnia and Hypocapnia on Intraoperative Blood Loss and Quality of Surgical Field During Functional Endoscopic Sinus Surgery

BACKGROUND:Anesthetic management during functional endoscopic sinus surgery is aimed at minimizing bleeding and establishing a near-perfect surgical field. We investigated whether deliberate intraoperative hypercapnia and hypocapnia may affect blood loss and quality of surgical field through a proposed modulating effect of different carbon dioxide (CO2) tension levels on nasal vasculature. METHODS:One hundred and eighty patients were randomly assigned to normocapnia (end-tidal CO2 [ETco2] 37 ± 2 mm Hg), hypercapnia (ETco2 60 ± 2 mm Hg), and hypocapnia (ETco2 27 ± 2 mm Hg) groups. Anesthetic management was with propofol and remifentanil infusions, nitrous oxide, and moderate controlled hypotension. Blood loss and operating conditions were assessed by the surgeon who was blinded to group assignment. Differences among the study groups, the effect of the study group and time on ETco2 levels and hemodynamic variables, and the association of blood loss with surgical covariates were analyzed. RESULTS:There were no differences in blood loss and quality of surgical field among the study groups. Patients in the hypocapnia group demonstrated the highest, and in the hypercapnia group, the lowest, requirements for remifentanil, labetalol, and administration of the antihypertensive medications in general. The computed tomography-graded severity of sinonasal disease and duration of surgery were the only independent predictors of intraoperative blood loss. CONCLUSIONS:CO2 management during functional endoscopic sinus surgery does not influence operating conditions or blood loss.

Is it More Difficult to Cannulate the Right Internal Jugular Vein in Morbidly Obese Patients than in Nonobese Patients

BackgroundThe placement of an internal jugular vein (IJV) catheter is considered to be more difficult in morbidly obese patients. The objective of this study was to compare the success of simulated IJV puncture between morbidly obese patients and a nonobese control group.MethodsThirty-four morbidly obese patients with body mass index (BMI, kg/m2) ≥40 were compared with 36 patients with BMI < 30. Right IJV puncture was simulated using an ultrasound probe directed towards the sternal notch at the midpoint between the sternal notch and the mastoid process. The investigator placing the probe was blinded as to the image being created on the ultrasound machine. Success rate was assessed at three different head rotation angles from midline; 0°, 30°, and 60°.ResultsThere was no statistically significant difference in successful simulated IJV puncture between two groups for any of the head positions. However, there was a higher incidence of the carotid artery (CA) puncture in the morbidly obese patient group when the head rotation was advanced from neutral position to 60° (p < 0.05). In addition, the ultrasound showed significantly more overlapping of the IJV over the CA in morbidly obese patients at 0° (p < 0.05) and 30° (p < 0.05). Our results show no statistically significant difference in success rate of IJV puncture between morbidly obese patients and nonobese patients. Keeping the head in a neutral position in morbidly obese patients minimizes the overlapping of the IJV over the CA and the risk of CA puncture.ConclusionHowever, due to the fact that even in the neutral position there is a significant increase in overlap between IJV and CA, we recommend the use of ultrasound guidance for IJV cannulation in obese patients.

Pharmacology and obesity.

Dosing of anesthetic agents in the morbidly obese patient differs significantly from that of the normal size patient. Until recently, obese subjects have been routinely excluded from clinical trials to obtain regulatory approval for investigational drugs. This has resulted in package insert dosage recommendations based on total body weight (TBW), valid for normal weight patients but not for the obese. Well-planned and rational management of morbidly obese patients undergoing surgery requires detailed knowledge of how morbid obesity affects drug dosing. Not only the increased body size and different body composition but also the physiological changes and comorbidities impact safe drug dosing by the anesthesiologist. The aim of this review is to provide the anesthesiologist with a practical approach to drug dosing in the morbidly obese patients.

Anesthetic drugs and bariatric surgery

The prevalence of obesity is increasing worldwide. For severely obese patients, bariatric surgery is the only effective option for sustained weight loss and associated health improvement. As a consequence, the number of bariatric surgical procedures being performed is growing exponentially. Systematic knowledge regarding the effect of obesity on the pharmacokinetics and pharmacodynamics of anesthetic agents is generally lacking, and data for morbidly obese (body mass index [BMI] 40–49 kg/m2)) and super-obese patients (BMI > 50 kg/m2) are almost completely non-existent. Most drug-dosing guidelines are based on results from relatively small studies in moderately obese patients. Future systematic pharmacological research is needed for improved and more rational peri-operative care of morbidly obese patients.

Do distribution volumes and clearances relate to tissue volumes and blood flows? A computer simulation.

BackgroundKinetics of inhaled agents are often described by physiological models. However, many pharmacokinetic concepts, such as context-sensitive half-times, have been developed for drugs described by classical compartmental models. We derived classical compartmental models that describe the course of the alveolar concentrations (FA) generated by the physiological uptake and distribution models used by the Gas Man® program, and describe how distribution volumes and clearances relate to tissue volumes and blood flows.MethodsGas Man® was used to generate FA vs. time curves during the wash-in and wash-out period of 115 min each with a high fresh gas flow (8 L.min-1), a constant alveolar minute ventilation (4 L.min-1), and a constant inspired concentration (FI) of halothane (0.75%), isoflurane (1.15%), sevoflurane (2%), or desflurane (6%). With each of these FI, simulations were ran for a 70 kg patient with 5 different cardiac outputs (CO) (2, 3, 5, 8 and 10 L.min-1) and for 5 patients with different weights (40, 55, 70, 85, and 100 kg) but the same CO (5 L.min-1). Two and three compartmental models were fitted to FA of the individual 9 runs using NONMEM. After testing for parsimony, goodness of fit was evaluated using median prediction error (MDPE) and median absolute prediction error (MDAPE). The model was tested prospectively for a virtual 62 kg patient with a cardiac output of 4.5 L.min-1 for three different durations (wash-in and wash-out period of 10, 60, and 180 min each) with an FI of 1.5% halothane, 1.5% isoflurane, sevoflurane 4%, or desflurane 12%.ResultsA three-compartment model fitted the data best (MDPE = 0% and MDAPE ≤ 0.074%) and performed equally well when tested prospectively (MDPE ≤ 0.51% and MDAPE ≤ 1.51%). The relationship between CO and body weight and the distribution volumes and clearances is complex.ConclusionThe kinetics of anesthetic gases can be adequately described e by a mammilary compartmental model. Therefore, concepts that are traditionally thought of as being applicable to the kinetics of intravenous agents can be equally well applied to anesthetic gases. Distribution volumes and clearances cannot be equated to tissue volumes and blood flows respectively.