|Year : 2019 | Volume
| Issue : 2 | Page : 192-199
Labetalol (preoperative oral and intraoperative infusion) overrides nitroglycerine infusion for hypotensive anesthesia during functional endoscopic sinus surgery
Alfred M Said, Heba B El-Serwi
Department of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||18-Nov-2017|
|Date of Acceptance||29-Nov-2018|
|Date of Web Publication||12-Jun-2019|
Heba B El-Serwi
7 El Shahid Ahmed Wasfi Street, Almaza, 11341, Cairo
Source of Support: None, Conflict of Interest: None
Objective The objective of this study was to evaluate preoperative and intraoperative changes of heart rate (HR) and blood pressure (BP) measures, amount of bleeding, surgical field visibility, and surgeons’ satisfaction during FESS performed under hypotensive anesthesia (HA) for mild hypertensive patients.
Patients and methods A total of 104 patients were randomly divided into two groups: group L included patients premedicated by 200 mg oral labetalol 2 h preoperatively and intraoperative labetalol infusion at a rate of 6 ml/min to provide 0.2 mg/kg/h. Group N included patients who received a placebo tablet 2 h preoperatively and nitroglycerine infusion at a rate of 21 ml/h to provide 0.5 µg/kg/min. The study outcome included control of induction and intubation-induced BP and HR responses throughout the surgery.
Results Labetalol premedication significantly decreased preoperative HR and BP than baseline measures and significantly reduced induction and intubation-induced pressor responses compared with placebo. The applied protocols of HA allowed significant reduction of BP, intraoperative bleeding, and improved field visibility that satisfied the surgeons. Labetalol infusion significantly lowered intraoperative HR and BP than baseline and preoperative measures. Labetalol infusion significantly lowered intraoperative HR compared with nitroglycerine infusion. Patients who received labetalol infusion had significantly lower HR and mean arterial pressure at the time of extubation and 1 h postoperatively compared with patients of group N.
Conclusion Oral labetalol premedication has effectively blunted induction and intubation-induced pressor reflex. Labetalol infusion effectively reduced intraoperative HR and BP, reduced intraoperative bleeding, and improved field visibility during FESS better than nitroglycerine infusion. Labetalol significantly improved emergence from anesthesia with maintenance of significantly lower postoperative HR and BP than patients who received nitroglycerine.
Keywords: functional endoscopic sinus surgery, labetalol hypotensive anesthesia, nitroglycerine infusion, oral labetalol, surgical field visibility
|How to cite this article:|
Said AM, El-Serwi HB. Labetalol (preoperative oral and intraoperative infusion) overrides nitroglycerine infusion for hypotensive anesthesia during functional endoscopic sinus surgery. Res Opin Anesth Intensive Care 2019;6:192-9
|How to cite this URL:|
Said AM, El-Serwi HB. Labetalol (preoperative oral and intraoperative infusion) overrides nitroglycerine infusion for hypotensive anesthesia during functional endoscopic sinus surgery. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Oct 14];6:192-9. Available from: http://www.roaic.eg.net/text.asp?2019/6/2/192/260152
| Introduction|| |
Chronic rhinosinusitis (CRS) refractory to medical and nonsurgical treatments is a challenge . Functional endoscopic sinus surgery (FESS) could be considered as the standard treatment of refractory CRS . Despite being a minimally invasive technique, small bleeding areas can reduce operative visibility during FESS resulting in the destruction of the surrounding structures . Deliberate hypotension using a range of pharmacological agents during general anesthesia reduces blood loss with subsequent improvement of field visibility .
Mild hypertension was defined as a blood pressure (BP) level of 140–159 mmHg systolic and/or 90–99 mmHg diastolic . Most of mild hypertension patients are free of subjective symptoms except elevated BP; however, some of these patients develop cardiovascular events , a risk that can be significantly reduced by lowering systolic BP below the cutoff of 140 mmHg . Results of meta-analysis provide strong support for lowering systolic BP to less than 130 mmHg to significantly reduce the vascular risk and comorbidities . Lifestyle modifications for reducing BP are appropriate for all patients  and may be recommended while delaying drug treatment for those at lower absolute levels of cardiovascular disease risk .
Labetalol is a combined nonselective β-adrenoceptor antagonist and a competitive antagonist of postsynaptic α1-adrenoceptors . In humans, the ratio of β : α-antagonism is 3 : 1 after oral  and 7 : 1 after intravenous administration . Oral labetalol is readily absorbed in humans with a 25% absolute bioavailability . Peak plasma level was achieved after 2.5 and 20–120 min after intravenous and oral administration, respectively  with a peak plasma effect within 1–4 h after oral intake  and elimination half-life of 5–8 h .
Hypertensive patients are more liable to bleed during surgery. Hypotensive anesthesia (HA) could improve the anesthetic outcome and field visibility during FESS, especially in hypertensive patients. Preanesthetic medication with oral labetalol and intraoperative intravenous labetalol infusion can induce HA comparable to intraoperative nitroglycerine infusion.
The study targets to evaluate preoperative and intraoperative changes of heart rate (HR) and BP measures, amount of bleeding, surgical field visibility, and surgeons’ satisfaction during FESS performed for hypertensive patients.
A prospective, comparative study.
University Hospital, Cairo, Egypt.
| Patients and methods|| |
This study was conducted at the Anesthesia and Otorhinolaryngology Departments, Ain Shams University Hospital since June 2015 till November 2016. The study protocol was approved by the local ethics committee. Inclusion criteria included refractory CRS in mild hypertensive patients maintained on lifestyle change for control of BP with no regular antihypertensive therapy. Refractory CRS was defined according to the guidelines of the American Academy of Otolaryngology − Head & Neck Surgery (AAOHNS), which included objective confirmation of inflammation on either endoscopy or computed tomographic imaging . Exclusion criteria included medically controlled hypertension, cardiovascular, hepatic or renal diseases, bleeding diathesis, maintenance on aspirin or other medications affecting coagulation or anemia with hemoglobin concentrations of less than 10 g/dl.
All patients underwent demographic data collection, full clinical and radiological examination of paranasal sinuses, and clinical examination for evaluation of BP measures, American Society of Anesthesiologists (ASA) grade, and for presence of other morbidities to assure inclusion and exclusion criteria. A total of 104 patients fulfilling inclusion criteria and signed, written fully informed consent were randomly given, using sealed envelopes prepared by a blinded assistant and chosen by the patient himself/herself, who were divided into two groups: group L included 52 patients who were premedicated by 200 mg oral labetalol (Trandate tablet, 100 mg tablet; Aspen Pharmacare, Durban, South Africa) received with small amounts of water 2 h preoperatively at the preanesthetic unit and group N included 52 patients who received a placebo tablet 2 h before surgery. All patients underwent determination of baseline HR, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure (MAP) before oral tablet intake (T1) and 2 h thereafter (T2) and then the patients were transferred to the operating room. All patients were noninvasively monitored for HR and BP measures. Patients of both groups received the same anesthetic protocol including induction of anesthesia by propofol 2 mg/kg, followed by cisatracurium (0.15–0.2 mg/kg) to facilitate tracheal intubation and controlled ventilation was adjusted to an end-tidal CO2 concentration of 30–35 mmHg. Fentanyl injection (0.15–0.2 µg/kg) was also given to all patients at induction. Anesthesia was maintained in both groups by sevoflurane 1.0–1.5 MAC with 100% oxygen. HR and BP measures were determined after induction (T3) and intubation (T4) in both groups. Then, intravenous infusions prepared for each group were started till 5 min before the end of surgery targeting for MAP of 55–60 mmHg. HR and BP measures were determined and recorded every 15 min (T5) till the infusion was stopped (T6), at the time of tracheal extubation (T7) and 1 h postoperatively (T8). Both the anesthetist and the surgeon were blinded about the type of infusion that was prepared by the blinded assistant.
Preparation of infusions
- Labetalol infusion was prepared according to the manufacturer’s instruction by mixing 4 ml labetalol (Trandate injection, 5 mg/ml; Aspen Pharmacare) in 500 ml saline to obtain a final concentration of 0.04 mg/ml. Infusion rate was adjusted at 6 ml/min provide 0.2 mg/kg/h  for a patient weighing 70 kg.
- Nitroglycerine infusion was prepared according to the manufacturer’s instruction by dissolving 50 mg nitroglycerine (Fliptop Vial 5 ml 25 mg; Hospira Inc., Lake forest, Illinois, USA) in 500 ml saline to obtain a final concentration of 100 µg/ml. Infusion rate was adjusted at 21 ml/h to provide 0.5 µg/kg/min for a patient weighing 70 kg .
Control of hemodynamic responses during induction of anesthesia and throughout the surgery.
- Duration of surgery, amount of bleeding, and need for transfusion.
- Surgeon satisfaction evaluated as very satisfied, satisfied, good, dissatisfied, or very dissatisfied.
- Frequency of postoperative bleeding.
- Postoperative pain scoring using a 10-point visual analog scale.
- Surgical field visibility was graded using a six-point score with 0 indicating no bleeding and 5 indicating severe bleeding and constant suctioning is required; otherwise surgery is hardly possible or impossible at all .
The sample size was calculated using the standard nomogram proposed by Kraemer and Thiemann  and a sample size of at least 40 patients per group was determined to be sufficient to detect a difference at the 5% significance level and give the trial 80% power. The results were analyzed using the paired t-test and one-way analysis of variance with post-hoc Tukey’s honest significance test and χ2-test). Statistical analysis was conducted using the SPSS (version 15, 2006; SPSS Inc., Chicago, Illinois, USA) for Windows Statistical Package. A P value of less than 0.05 was considered significant.
| Results|| |
The study included 104 patients; 70 men and 34 women with a mean age of 43.3±7.5; range: 28–55 years. Seventy-five patients were of ASA grade I and 29 patients were of ASA grade II. Patients’ enrollment data showed nonsignificant difference between both groups as shown in [Table 1].
Patients who received oral labetalol had significantly reduced preoperative HR compared with their baseline rate and compared with preoperative HR of patients of group N. Induction of anesthesia and tracheal intubation significantly increased HR in patients of both groups compared with baseline and preoperative HR. However, preoperative oral labetalol significantly reduced the extent of such increase of HR compared with placebo. Intraoperative infusions significantly reduced intraoperative HR in patients of both groups compared with their HR recorded at T1, T3, and T4. Intraoperative HR was significantly lower in patients of group N, but nonsignificantly lower in patients of group L compared with T2 HR. Intraoperative HR records were significantly lower in patients of group L compared with patients of group N. Extubation induced increased HR in patients of both groups compared with their intraoperative records with significantly higher HR in patients of group N than patients of group L. HR recorded at T7 and T8 was significantly lower in both groups compared with the HR recorded at T1–T4 ([Table 2] and [Figure 1]).
|Table 2 Heart rate measures of patients of both groups compared with baseline and preoperative data|
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|Figure 1 Mean heart rate (HR) recorded in patients of both groups throughout the study duration.|
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Baseline (T1) BP measures showed nonsignificant difference between patients of both groups. However, BP measures recorded at T2–T4 were significantly lower in patients of group L compared with patients of group N. Intraoperative BP measures till the time of infusion termination were nonsignificantly lower in patients of group N compared with patients of group L. In contrast, BP measures at the time of extubation and 1 h postoperatively were significantly lower in patients of group L compared with patients of group N. BP measures recorded at the time of induction of anesthesia and intubation were significantly higher in patients of group N than baseline and preoperative measures in group N, while were significantly lower compared with baseline measures. Intraoperative BP measures recorded for all patients were significantly lower compared with their respective T1–T4 measures. BP measures recorded at the time of extubation and 1 h postoperatively were significantly lower compared with T1–T4 measures, but were significantly higher compared with T5–T6 measures in patients of both groups ([Table 3] and [Figure 2]). Operative data and surgeon’ satisfaction scoring showed a nonsignificant difference between both groups as shown in [Table 4].
|Table 3 Blood pressure measures of patients of both groups compared with baseline and preoperative data|
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|Figure 2 Mean arterial pressure (MAP) recorded in patients of both groups throughout the study duration.|
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| Discussion|| |
Significant bleeding during FESS impairs recognition of anatomical references and may negatively affect the surgical outcome ; this fact indicates the necessity for the use of HA and support the hypothesis of this study. The applied protocol of HA for both groups allowed significant reduction of BP measures with subsequent reduction of intraoperative bleeding and improved field visibility that satisfied the surgeons and prevented case canceling in both groups.
These findings go hand in hand with previous studies which evaluated HA during FESS using multiple drugs ,,,, or anesthetic procedures , and found that HA decreases intraoperative bleeding, enhances surgical field quality, and is beneficial in providing good visibility during FESS with hemodynamic stability and smooth rapid emergence.
Labetalol premedication significantly decreased preoperative HR and BP measures compared with baseline measures and significantly reduced induction and intubation-induced pressor response compared with patients of other groups who received placebo. These findings spot light on the possibility of preoperative preparation by labetalol especially in this patients’ population with high preoperative BP measures. Similarly, Singh et al.  found esmolol (0.5 mg/kg) and labetalol (0.25 mg/kg) given both at 2 and 5 min before intubation significantly attenuated the rise in HR and systolic arterial pressure during laryngoscopy and intubation, but documented that labetalol is better than esmolol in attenuating the sympathomimetic response to laryngoscopy and intubation. Also, Do et al.  demonstrated that administration of intravenous labetalol is effective in attenuating tracheal intubation-induced hemodynamic responses. Moreover, Meftahuzzaman et al.  reported that preoperative labetalol is better than fentanyl for attenuation of laryngoscopic and intubation reflex and El-Shmaa and El-Baradey  found that preoperative intravenous injection of labetalol or dexmedetomidine significantly decreased HR and MAP during laryngoscopy and intubation than control patients.
In support of the use of oral preoperative premedication to control intubation-induced hemodynamic responses and intraoperative bleeding, oral clonidine in varied doses was used for a similar target and provided hemodynamic stability, bleeding control, decrease of operative time, and enhancement of surgical results ,,. Also, Rahimzadah et al.  reported that patients who received metoprolol the night before surgery and on the day of the surgery had slight bleeding during surgery and Amr and Amin  found premedication with oral atenolol 50 mg twice/day for 1 day before HA with sodium nitroprusside during spinal surgeries is clinically safe and effective to reduce HR, the amount of sodium nitroprusside used, amount of blood loss, and amount of blood transfused with better quality of the surgical field.
Labetalol infusion significantly lowered intraoperative HR and BP measures compared with baseline and preoperative measures with nonsignificant difference between intraoperative measures. Labetalol infusion induced hypotension without concomitant tachycardia with significantly lower intraoperative HR as compared with HR records of patients who received nitroglycerine infusion till the end of infusion. In line with these findings, Hadavi et al.  reported a little difference between labetalol and nitroglycerine on the effect of intraoperative blood loss and surgical field quality in rhinoplasty surgery and Sajedi et al.  found that infusion of labetalol and remifentanil after a bolus dose can induce effective, controlled hypotension under general anesthesia during FESS.
Interestingly, patients who received labetalol infusion had significantly lower HR and MAP at the time of extubation and 1 h postoperatively compared with patients who received nitroglycerine infusion. This finding could be attributed to the difference in pharmacokinetic properties of both drugs as Wester et al.  reported biexponential decline in plasma nitroglycerine concentration after intravenous administration with an initial and terminal half-lives of 0.8 and 18 min (2–5 and 5–60 min postadministration), respectively, and Bauer and Fung  detected rebound elevations of left ventricular end-diastolic pressure to about 25% above baseline values, at 30–60 min after abrupt nitroglycerin infusion termination. In contrast, the half-life of the elimination phase of labetalol in the plasma varied between 5 and 14 h after oral and between 3.9 and 6.3 h after intravenous administration . Thus, the currently reported significant difference between patients who received labetalol or nitroglycerin infusion after infusion termination could be attributed to the continued effect of the preoperative oral dose coupled with the effect of the infusion; so BP was under strict control with labetalol than with nitroglycerin.
| Conclusion|| |
Premedication with oral labetalol is an effective method to blunt induction and intubation-induced pressor reflex. Labetalol infusion effectively reduced intraoperative HR and BP measures with subsequent reduction of intraoperative bleeding and improved field visibility during FESS better than nitroglycerine infusion. Labetalol significantly improved emergence from anesthesia and maintained postoperative control of HR and BP measures significantly than patients who received nitroglycerine.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]