Abstract
Objectives
The aim of the study is to investigate the efficacy of different dosages of single bolus propofol administered on the basis of total body weight or corrected body weight for the intravenous induction of anesthesia in obese patients undergoing bariatric surgery.
Materials and methods
Thirty-eight obese patients with a body mass index (BMI) of 30 kg/m2 or greater were randomly divided into two groups. They received single-bolus propofol (2 mg/kg) for intravenous induction of anesthesia based on either total body weight (TBW; 20 patients) or corrected body weight 60% (CBW60; 18 patients). Patients’ characteristics, biochemical data, monitored bispectral index (BIS) values, and hemodynamic parameters were compared between the two groups.
Results
The propofol dose was significantly lower in the CBW60 group than in the TBW group (189.5 ± 36.3 mg vs. 217.3 ± 39.1 mg, respectively; p = 0.03). The highest BIS value, representing potential awareness after intubation, was relatively higher in the CBW60 group, but this difference was not statistically significant (CBW60 group, 53.6 ± 11.1; TBW group, 48.6 ± 8.1; p = 0.22). Eighty-three percent of patients experienced hypotension during induction and at least 44% patients showed marked hypotension. There was no significant difference between the TBW and CBW60 groups in blood pressure after intubation.
Conclusion
When using single bolus propofol, the CBW60 group showed similar BIS values and hemodynamic effects as the TBW group during the intravenous induction of general anesthesia for obese patients.
Keywords
electroencephalography; bispectral index; obesitypropofol;
1. Introduction
The prevalence of obesity has been increasing over the past few decades, and the trend is rising in the United States and in Asian countries such as Taiwan.1, 2 The increased prevalence of obesity is highly coexistent with medical conditions such as type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, and asthma; therefore obesity promotes increased mortality.3, 4, 5
The increasing number of obese patients has resulted in an increasing demand for obesity-related surgical procedures in this specific population.6, 7, 8, 9 The effects of obesity on metabolic, cardiovascular, and pulmonary functions increase the risks of using anesthesia in these patients.10, 11, 12Intubation of obese individuals is a challenge for anesthesiologists because desaturation can occur rapidly in obese patients after apnea. To secure the safety of these patients, it is imperative to shorten the induction–apnea period to avoid possible desaturation.
Propofol is a commonly used intravenous anesthetic for the induction of anesthesia in surgery. Current studies on anesthesia for obese patients are primarily focused on specific infusion models such as total intravenous anesthesia or target-controlled infusion.13 In the rapid infusion model, morbidly obese individuals receive propofol, based on total body weight (TBW), to provide a shorter induction time. Compared to normal weight individuals, morbidly obese individuals who are administered propofol based on lean body weight (LBW) for the induction of anesthesia demonstrated a similar onset for loss of consciousness; this may be explained by the unchanged initial volume of distribution, based on LBW.13, 14, 15, 16However, the optimal dosage of propofol with the rapid infusion model for bolus intravenous administration for this specific population remains controversial. We performed a prospective, randomized controlled study to evaluate the clinical efficacy of two different dosages of propofol—calculated by TBW or by corrected body weight 60% (CBW60)—for the induction of anesthesia by single-bolus intravenous administration in obese patients undergoing bariatric surgery.
2. Materials and methods
2.1. Ethics approval
The study was evaluated and approved by the Human Subjects Joint Institutional Review Board of the Taipei Medical University (Taipei, Taiwan) and was performed pursuant to the recommendations of the Helsinki Declaration.
2.2. Patients
Forty obese patients were studied. They were classified as having American Society of Anesthesiologists (ASA) physical status I or II, were aged 18–59 years, and were scheduled for elective bariatric procedures that are performed under endotracheal general anesthesia (e.g., laparoscopic gastric banding, sleeve gastrectomy, and Roux-en-Y bypass surgery). Exclusion criteria included patients who were expected to have a difficult airway or were scheduled for awake fiberoptic intubation; patients with known severe cardiopulmonary dysfunction, impaired hepatic or renal function, suspected allergy to the study drugs, extreme anxiety; or patients whose preoperative medication regimen included benzodiazepines, opioids, or over-the-counter sleep medications.
2.3. Definition and data collection
Each patient was assessed by the Biospace InBody 230 body impedance scale (Biospace Co., Seoul, South Korea) with a maximum weight of 551 lbs (250 kg). Of the 40 patients, six patients had Class I obesity [i.e., body mass index (BMI) of 30.0 kg/m2 to 34.9 kg/m2]; 12 patients had Class II obesity (i.e., BMI of 35.0 kg/m2 to 39.9 kg/m2); and 22 patients had Class III obesity (BMI of 40 kg/m2 or greater). Intraoperative hypotension was defined as a greater than 20% decrease from the baseline systolic or diastolic blood pressure during induction. Marked hypotension was defined as a greater than 30% decrease from the baseline systolic or diastolic blood pressure during induction. We also defined a bispectral index (BIS) value of greater than 60 as indicative of possible intraoperative awareness. Patients were randomly assigned to one of two study groups for the induction of general anesthesia. The TBW group received propofol at 2 mg/kg by total body weight. The CBW60 group received propofol 2 mg/kg by corrected body weight 60% [CBW60 = LBW + (TBW – LBW) × 60%].
2.4. Anesthesia procedure
A 20-gauge peripheral IV catheter connected to a T-piece tubing was placed in the patient’s left or right forearm. No premedication was given and all obese patients were placed in the “ramped” position.17 Standard hemodynamic and oxygen saturation monitors were applied in the usual manner and a BIS standard sensor (Aspect Medical Systems, Newton, MA, USA) was attached to the patients’ forehead. Except for the anesthesiologist who administered the induction dose of propofol, all other medical personnel and the patients were blinded to the propofol induction dose protocol.
Each patient was asked to hold a 20-mL saline-filled syringe between their thumb and little finger and instructed not to drop the syringe.14 After preoxygenation for 3 minutes through a facemask, all patients were intravenously administered fentanyl (2–3 μg/LBW) and lidocaine (100 mg). The obese patients were then randomly assigned to the TBW group or the CBW60 group to receive the designated dose of propofol. Propofol was administered in an intravenous bolus through the T-piece tubing within 15 seconds. The onset of loss of consciousness was determined when the patient dropped the syringe, at which point the time was recorded. After dropping the syringe, the patient was asked to open his or her eyes and the eyelash test was performed by the blinded medical personnel. The anesthesiologist was allowed to give an additional bolus of propofol until loss of consciousness was achieved.
After the propofol injection, succinylcholine (1 mg/TBW) was administered for endotracheal intubation. Anesthesia was maintained with 3% sevoflurane in 50% oxygen-air mixture (6 L/min) for the first 5 minutes. After that, all settings could be adjusted to suit the surgical condition.
The ventilation was mechanically controlled by using a nonrebreathing system to maintain an end-tidal partial pressure of carbon dioxide between 32 mmHg and 35 mmHg. We used cisatracurium to maintain neuromuscular blockade. The depth of anesthesia was assessed by a BIS monitor (Module 90482, Ultraview Bispectral Index; Spacelabs Medical, Snoqualmie, WA, USA).18
2.5. Measurements
Heart rate, oxygen saturation (SpO2), and blood pressure data were recorded at one-minute intervals after the propofol was injected, and BIS data were recorded every 15 seconds for the first 10 minutes. Intubation time, additional propofol administered during induction, use of inotropic or vasopressor drugs, and hemodynamic variables (e.g., heart rate, blood pressure) were also recorded. After the completion of the surgery, the patients were transferred to the postoperative recovery unit. To determine whether perioperative awareness had occurred, the patients were interviewed 60–90 minutes after emergence from anesthesia to answer questions on the Brice questionnaire.19
2.6. Statistical analysis
We used the Wilcoxon rank sum test and the Chi-square test to compare the difference between the TBW and CBW60 groups in the average and the categorical data. The incidence of marked hypotension, possible awareness, and BIS values less than 40 were also compared between the two groups by using the Chi-square test. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratios (ORs) and the 95% confidence intervals (CIs) of postinduction hypotension associated with TBW (data not shown). SAS software version 9.1 (SAS Institute Inc., Cary, NC, USA) was used for data analyses with two-sided probability, and p < 0.05 was considered statistically significant.
3. Results
Of the 40 patients who were enrolled in this study (from March 1, 2012 to May 31, 2012), 38 patients completed the study. Two patients were excluded because of incomplete data collection or because they had undergone multiple endotracheal intubation attempts. Table 1 shows the demographic characteristics of the patients. There were no significant differences between the TBW group and the CBW60 group in age, sex, body composition, BMI, comorbidities, and lifestyle. Table 2 shows the details of the patients' biochemical data. When compared with the TBW group, the CBW60 group showed no significant differences in complete blood count, coagulation profile, liver function, renal function, electrolytes, total cholesterol, triglyceride, high-density lipoprotein, uric acid, or blood sugar data. As Table 3 shows, the average BIS values after intubation were higher at several time points in the CBW60 group than in the TBW60 group. For example, at 165 seconds, the BIS values were 44.2 ± 8.2 (CBW60 group) and 38.7 ± 4.5 (TBW group), p = 0.0143; at 180 seconds, the BIS values were 44.1 ± 7.6 (CBW60 group) and 39.3 ± 4.5 (TBW group), p = 0.0216; at 240 seconds, the BIS values were 42.7 ± 7.0 (CBW60 group) and 38.1 ± 4.7 (TBW group), p = 0.0268; and at 345 seconds, the BIS values were 40.7 ± 6.0 (CBW60 group) and 37.0 ± 0.7 (TBW group), (p = 0.0467). Fig. 1 shows the time-dependent average BIS values for both groups. There were no average BIS values higher than 60. Compared to the TBW group, the CBW60 group showed a consistent trend of slightly higher average BIS values.
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The systolic and diastolic blood pressure values after intubation did not significantly differ between the two groups (Table 4). The average dose of propofol did significantly differ between the TBW and CBW60 groups during the induction period (217.3 ± 39.1 mg vs. 189.5 ± 36.3 mg, respectively, p = 0.03; Table 5). The highest postintubation BIS value was higher in the CBW60 group [53.6 ± 11.1 (CBW60) vs. 48.6 ± 8.1 (TBW), p = 0.22], but this difference was of no statistical significance. There was no significant difference between the groups in potential awareness after intubation; however, possible awareness was experienced by more patients in the CBW60 group (9.1%, N = 4) than in the TBW group (5.6%, N = 1) (p = 0.34). At least 80% of patients in both groups had a BIS value lower than 40, but the difference between the groups was of no statistical significance.The systolic and diastolic blood pressure values after intubation did not significantly differ between the two groups (Table 4). The average dose of propofol did significantly differ between the TBW and CBW60 groups during the induction period (217.3 ± 39.1 mg vs. 189.5 ± 36.3 mg, respectively, p = 0.03; Table 5). The highest postintubation BIS value was higher in the CBW60 group [53.6 ± 11.1 (CBW60) vs. 48.6 ± 8.1 (TBW), p = 0.22], but this difference was of no statistical significance. There was no significant difference between the groups in potential awareness after intubation; however, possible awareness was experienced by more patients in the CBW60 group (9.1%, N = 4) than in the TBW group (5.6%, N = 1) (p = 0.34). At least 80% of patients in both groups had a BIS value lower than 40, but the difference between the groups was of no statistical significance.
The proportion of patients in the two groups with hypotension or marked hypotension was not significant (Table 5). At least 44% of all patients experienced marked hypotension and at least 83% of all patients experienced hypotension. The patients experiencing postintubation hypotension were successfully treated with vasoactive drugs (e.g., ephedrine, norepinephrine). There was no significant difference between the two groups in the use of vasoactive drugs. There were no other side effects during anesthetic induction. On questioning the patients during the postoperative interview, none reported intraoperative awareness or recall (data not shown).
4. Discussion
In this prospective randomized controlled trial, different weight-based formulae of single-bolus injection of propofol were applied and assessed during intravenous induction in obese patients. There were no significant differences between the two groups in postintubation blood pressure (systolic or diastolic) or in the proportion of patients experiencing potential awareness (based on a high BIS value). The proportion of patients with hypotension or marked hypotension was similar in both groups.
Pharmacokinetic concerns during drug administration in obese patients confounded the dosing strategy. Whether lean body weight or total body weight is used, the calculation of the dose remains controversial. Despite current knowledge, there is no conclusive superiority of a specific model when applying a target-controlled infusion model. The pharmacokinetic models of Marsh and Schnider were developed without taking into consideration the specificity for obese or morbidly obese patients. Regardless of which model is used, there is no definite scientific evidence showing any reliable pharmacokinetic predictive model that could be safely used for obese or morbidly obese patients.20 Because of the uncertainty of effectiveness and the high cost of target-controlled infusion devices, anesthesiologists may have limited their use in obese patients. Recently, 60 morbidly obese patients were administered propofol through rapid infusion at the rate of 100 mg/(kg × h) based on LBW or TBW for the induction of anesthesia. Morbidly obese individuals receiving propofol infusion based on TBW needed a significantly larger dose with rapid onset to loss of consciousness.14
In obese patients, the TBW is much higher than the LBW. Previous studies show the initial volume of distribution is not modified in obese patients.15Studies focusing on a single bolus injection of propofol in obese individuals are lacking. The studies that document the use of single bolus injection of propofol are primarily limited to normal weight individuals.21, 22 The LBW may be an ideal weight scalar. However, there are concerns about the risk of potential awareness because little is known about single bolus propofol induction in obese individuals.
We used the CBW60 instead of the LBW in conducting this study to evaluate the efficacy of a single bolus of propofol at TBW and at CBW60 for induction in obese individuals. In our study, there were no significant differences between the two groups in potential awareness (as suggested by a high BIS value after intubation).
Induction of anesthesia in obese patients may be complicated by a reduced functional residual capacity, increased closing capacity, and the possibility of gastroesophageal reflux.23 Rapid sequence induction or shortening the induction period should be advocated when choosing general anesthesia for these patients.
Propofol was administered in this study by intravenous bolus injection under the dosage traditionally calculated by TBW in current clinical settings. This allowed a rapid loss of consciousness with a side effect (e.g., hypotension). In this study, at least 83% of patients experienced hypotension and at least 44% of patients experienced marked hypotension. Our study had a much higher rate of hypotension, compared to a previous study in which hypotension was experienced by 16.7% of patients in the LBW group and 30% of patients in the TBW group.14 The definition of hypotension used in previous study was a 40% decrease in the baseline mean arterial blood pressure within 5 minutes of propofol infusion. This definition is more rigorous and less commonly used in clinical settings. In our opinion, the definitions we used for hypotension and marked hypotension are close to what is used in daily practice and showed the possibility of hypotension as a severe side effect and showed a high percentage of hypotension.
There are several strengths in this study. First, we compared a wide range of sociodemographic factors, physical examination data, history of disease, and lifestyle in patients who underwent bariatric surgery. Second, between the two groups, we validated detailed biochemical measures that included complete blood count; a coagulation profile; liver function; renal function; and levels of electrolytes, total cholesterol, triglyceride, high-density lipoprotein, uric acid, and preoperative blood sugar. These were not assessed in previous studies. Third, we used BIS monitoring to facilitate and define the depth of anesthesia. Using BIS monitoring to indicate anesthesia depth or consciousness would allow optimization of drug delivery individually to avoid unnecessary deep anesthesia because of overdosage or light anesthesia from underdosage of hypnotics.18, 24, 25 Fourth, in the recent decade, studies regarding obese individuals for the induction of anesthesia have been primarily based on total intravenous anesthesia or target-controlled infusions. There are fewer concerns in single bolus induction among the obese population. Single bolus induction is still a popular induction method in current practice, which is important to anesthesiologists. The optimal weight-based dosing scalar for single bolus propofol induction has not been validated. This scalar could provide obese patients rapid and effective induction with minimal side effects. Further studies could be based on different weight-based scalars to find the optimal dosage for the single bolus induction of propofol in the obese population.
There are several limitations in this study. First, we did not obtain information concerning the use of preoperative medications such as statin or steroids in surgical patients. However, the preoperative medication use may have been distributed equally in the current study between both cohorts. Second, because of the small number of patients enrolled in each group, we recognize the limitations of a low-powered study. Third, the serum levels of propofol between the different regimens in obese patients were not validated; therefore, we could not explain the outcomes as evidence-based. Fourth, we would need to evaluate more dose-response regimens to test which would be better for the minimal induction dose.
In conclusion, this prospective randomly controlled study demonstrated no significant differences between the TBW group and the CBW60 group in blood pressure or in the highest BIS value. The CBW60 group weight-based scalar could have a similar hypnotic effect as in the TBW group. Future studies should be based on a greater number of obese patients, different kinds of surgery, and more reduced-weight scalars to investigate the optimal and minimal weight-based dosing scalars for single bolus propofol induction in the obese population.