|Year : 2020 | Volume
| Issue : 2 | Page : 161-166
Pregabalin effects on hypotensive anesthesia during spine surgery
Alaa Mazy, Maha A Abo-Zeid
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||19-Jul-2019|
|Date of Acceptance||12-Jan-2020|
|Date of Web Publication||27-Jun-2020|
MD Maha A Abo-Zeid
Department of Anesthesia and Surgical Intensive Care, Faculty of Medicine, Mansoura University, Mansoura, 35516
Source of Support: None, Conflict of Interest: None
Background Elective lumbar spine surgeries are commonly performed under controlled hypotensive general anesthesia to ameliorate intraoperative blood loss and improve the surgical field.
Purpose To demonstrate the effect of preoperative 150 mg oral pregabalin on facilitation of induced hypotension during spine surgery evaluated by the total intraoperative consumption of nitroglycerin required to maintain the targeted mean arterial blood pressure.
Patients and methods This prospective, randomized, controlled, double-blinded study included two groups of adult patients, who had undergone elective spinal surgery: the pregabalin group (n=53): received oral pregabalin capsule 150 mg 1 h before general anesthesia and the control group (n=53): received oral placebo capsule. The intraoperative invasive mean arterial blood pressure was maintained at the targeted range of 55–65 mmHg by nitroglycerin infusion titration. The intraoperative hemodynamics, blood loss and postoperative sedation, pain scores, and morphine consumption were recorded.
Results There was a statistically significant decrease in the consumption of both intraoperative nitroglycerin and postoperative morphine in the pregabalin group compared with the control group, but there was no concomitant decrease in intraoperative blood loss. Also, there was a statistically significant suppression of stress response to intubation in the pregabalin group.
Conclusion Premedication with oral 150 mg pregabalin before elective spinal surgery facilitated induced hypotension. Furthermore, it attenuated the stress response to tracheal intubation and enhanced postoperative analgesia.
Keywords: hypotensive anesthesia, pregabalin, spine surgery
|How to cite this article:|
Mazy A, Abo-Zeid MA. Pregabalin effects on hypotensive anesthesia during spine surgery. Res Opin Anesth Intensive Care 2020;7:161-6
| Introduction|| |
Elective lumbar spine surgeries are commonly performed under controlled hypotensive general anesthesia to improve the surgical field and decrease the blood loss ,. Deliberate hypotension could be achieved via various medications such as esmolol, remifentanil, sodium nitroprusside , nitroglycerin , and inhalational anesthetics . These medications are found to be associated with various side effects.
Pregabalin is a gabapentinoid compound defined as (S)-3 aminomethyl-5-methylhexanoic acid. Pregabalin and its developmental predecessor gabapentin are structurally, but not functionally, related to the inhibitory neurotransmitter gamma-aminobutyric acid and by decreasing the excitatory neurotransmitter glutamate release, they block the hyperalgesia and central sensitization through binding to the α-2-δ subunit of the voltage-dependent calcium channels located in the spinal cord and the brain. Pregabalin was first generated as a spasmolytic and as an anticonvulsant agent but later its role was confirmed in the management of neuropathic pain .
The aim of this study was to evaluate the effect of preoperative oral pregabalin to facilitate induced hypotension during spine surgery, evaluated by the total intraoperative consumption of nitroglycerin required to maintain the mean arterial blood pressure (MAP) at the range of 55–65 mmHg.
Secondary outcomes were intraoperative hemodynamics particularly during tracheal intubation and blood loss, postoperative sedation, pain scores, and morphine consumption in the first 24 h. The hypothesis was that a single preoperative dose of pregabalin 150 mg will augment intraoperative deliberate hypotension that will be reflected on nitroglycerin consumption and intraoperative blood loss.
| Patients and methods|| |
This prospective, randomized controlled, double-blinded study was performed after approval from the Institutional Review Board, code number: R/17.07.107 and clinical trial registry (ID: NCT03301025).
Consented 106 adult patients, aged from 18 to 60 years, American Society of Anesthesiologists scores I–II admitted to undergo elective spinal surgery under general anesthesia were included in this study.
Patients on diuretic treatment, corticosteroids, pregabalin, gabapentin, anticonvulsants, antipsychotics, or any analgesics within 48 h before surgery or patients with a history of allergy to the study drugs were excluded. Also, pregnant or nursing women or patients with hypertension, peripheral neuropathy, cerebrovascular disease, endocrinal disease, bleeding abnormality, cardiac, hepatic, or renal impairment were also excluded.
Preoperatively, all patients were carefully assessed and Allen’s test was done to ensure good collateral of the radial artery and all the patients were fasting, abstaining from solid food at least 6 h. They were educated on the use of visual analog scale (VAS) to monitor their pain (where 0 represented no pain and 10 meant the worst possible pain) and preoperative VAS was recorded.
The patients were randomly divided using the closed envelope method into two groups: The pregabalin group (n=53) received oral pregabalin capsule 150 mg (Lyrica; Pfizer Company, Egypt) and the control group (n=53) received oral placebo capsule. Almost 1 h before induction of general anesthesia, Ringer’s intravenous infusion was started at 6 ml/kg/h and the patients received an oral capsule by the ward nurse according to randomization.
On arrival to the operating theater (nearly 1 h after receiving the study drug), preoperative Ramsay sedation scale (1=anxious, agitated, or restless; 2=cooperative, oriented, and tranquil; 3=respond only to verbal command; 4=brisk response to light tap or loud auditor stimulus; 5=sluggish response to light tap or loud auditor stimulus; and 6=no response to light tap or loud auditor)  was done. Subsequent to ECG and pulse oximetry monitoring, an arterial catheter was inserted into a radial artery after subcutaneous local anesthetic infiltration and then invasive MAP was also monitored and recorded. After adequate preoxygenation, general anesthesia was induced by intravenous fentanyl 1.5 μg/kg, propofol 2 mg/kg, and atracurium 0.5 mg/kg and then an appropriated size tracheal tube was inserted.
The ventilator settings were adjusted to maintain the end-tidal carbon dioxide tension at 30–35 mmHg. Anesthesia was maintained by isoflurane concentration 1.5%, with 40% oxygen in air and then intravenous infusion of fentanyl 0.03 μg/kg/min was started while atracurium 0.1 mg/kg incremental doses were given as required. Then the patients were turned into the prone position above pad support permitting free hanging of the abdomen.
Heart rate (HR) and invasive MAP were recorded; immediately postinduction (before tracheal intubation), then immediately, 3, and 5 min after tracheal intubation. Then the HR was recorded at 5, 30, 60, 90, 120, 150, 180, 210, and 240 min after the surgical incision.
By starting the surgical incision, an intraoperative target range of MAP between 55 and 65 mmHg was achieved by nitroglycerin infusion initiated at 0.5 μg/kg/min and then titrated for the targeted MAP.
Hypotension (MAP <55 mmHg) was treated by stopping nitroglycerin, and proper fluid administration. If persisted; noradrenalin was started at the rate of 50 μg/kg/min. Bradycardia (HR <50 beat/min.) was treated with 0.01 mg/kg/atropine intravenous increments.
Intraoperatively, Ringer’s intravenous infusion of 5–7 ml/kg/h was maintained and urine output more than 0.5 ml/kg/h was assured to exclude hypovolemia. The intraoperative blood loss was assessed by adding the blood collected in the suction bottle (after subtraction of the saline used for wash) to the divided weight of the used towels (after subtracting its original weight) on 1.055. The blood loss was replaced by further fluid or otherwise by transfusion of packed red blood cells only after the blood loss exceeded 10% of the estimated blood volume.
The nitroglycerin infusion was stopped after finial surgical hemostasis with a recording of the total utilized dose. Fentanyl infusion was stopped before starting wound closure. Isoflurane was closed after the last surgical suture and intravenous morphine 0.025 mg/kg was administered. After dressing, the patients were turned to the supine position and received 0.04 mg/kg neostigmine and 0.015 mg/kg atropine for reversal of the residual neuromuscular blockade.
Extubation was done after establishment of acceptable spontaneous respiration and the patients were transferred to the recovery room. The surgical duration was recorded from the surgical incision till the last suture.
Postoperatively, Ramsay sedation scale was assessed at 0, 2, and 6 h while VAS at 0, 2, 4, 6, 8, 12, and 24 h. When VAS more than or equal to 4, morphine intravenous 0.03 mg/kg was given with recording of the total postoperative morphine consumption in the first 24 h. Any adverse effects such as dizziness, headache, nausea, and vomiting were recorded.
Data entry and analyses were performed using the Statistical Package for the Social Sciences, Version 20 (SPSS Inc., Chicago, Illinois, USA). The data were examined for normal distribution using Shapiro–Wilk’s test. Continuous, parametric data were reported as mean±SD while median (interquartile range) was used for nonparametric values after that were compared by Mann–Whitney U test or χ2 test. Paired sample t test was used for the within-group comparison. The statistical significance level was set at P value less than 0.05.
A preliminary study was performed that involved 24 patients and according to intraoperative nitroglycerin consumption, two means 0.6485 and 0.6030 and two SD values of 0.09524 and 0.04971 μg/kg/min (in the control group and pregabalin group, respectively) were resulted. A priori test using the G power software program was used to calculate the sample size and the effect size was 0.5989502. Assuming an α error of 0.05, β error of 0.18 and a power of 82%, 96 patients were needed in each group. Allowing for a dropout of 10%, 53 patients were needed in each group.
| Results|| |
There was no significant difference in the demographic data ([Table 1]) between the two groups.
Nitroglycerin consumption was lower in the pregabalin group (P<0.001), where the median and interquartile ranges were; 0.57 (0.06 μg/kg/min) versus 069 (0.15 μg/kg/min) in the control group.
The median values (interquartile range) of the intraoperative blood loss were 600 (425 ml) in the control group and 600 (650 ml) in the pregabalin group.
Immediately after tracheal intubation, the MAP increased significantly in both groups in comparison with basal values. In the pregabalin group, the stress response (MAP) was significantly lower than the control group (P=0.003) ([Figure 1]). No case developed intraoperative hypotension.
|Figure 1 Mean arterial blood pressure of the studied groups (values are mean±SD). *Significance in comparison with the control group; †significance in comparison with the basal value in the control group; ‡significance in comparison with the basal value in the pregabalin group, P value less than or equal to 0.05.|
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After tracheal intubation, the HR increased significantly for 5 min in the control group, while only for 3 min in the pregabalin group. However, the rise was significantly higher in the control than the pregabalin group just after intubation (P=0.002) ([Figure 2]). No case developed bradycardia.
|Figure 2 Heart rate of the studied groups (values are mean±SD). *Significance in comparison with the control group; †significance in comparison with the basal value in the control group; ‡significance in comparison with the basal value in the pregabalin group, P value less than or equal to 0.05.|
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There was no statistical difference in VAS for pain or Ramsay sedation score, except early at recovery where both scores were significantly lower in the pregabalin than the control group ([Table 2], [Table 3]). The consumption of morphine in the first postoperative 24 h was significantly lower in the pregabalin group (6.2±2.4 mg) compared with the control group (7.4±2.8 mg) (P=0.027).
[Table 4] shows no significant difference in the incidence of complications between the studied groups.
| Discussion|| |
In this present study, oral 150 mg pregabalin premedication significantly facilitated hypotensive anesthesia and reduced the intraoperative nitroglycerin consumption with no consequent statistically significant decrease in intraoperative blood loss.
The blunted hemodynamic stress response was the first benefit of pregabalin in the present study. Rastogi et al.  also reported this result using the same dose of pregabalin. Similarly, Gupta et al.  used 150 mg pregabalin dose given at 75–90 min before laparoscopic cholecystectomy that was associated with intraoperative hemodynamic stability. In their study, the HR significantly decreased perioperatively, even during the stress of laryngoscopy and the MAP also significantly attenuated during laryngoscopy and pneumoperitoneum.
In another study Gupta et al.  who used the same dose of oral pregabalin showed a statistically significant attenuation of HR and MAP during laryngoscopy with intraoperative persevered stabilization when compared with the control group. This perioperative hemodynamic stability induced by pregabalin could be explained by the adequate sedation and analgesia properties including the modulation of visceral pain and central sensitization ,.
In a study of Gupta et al. , the use of pregabalin was associated with reduction of propofol and fentanyl utilization intraoperatively. This decreased intraoperative anesthetic and analgesic consumption may explain the reduced nitroglycerine consumption in the pregabalin group in this study.
In the current study, nitroglycerin consumption was lower in the pregabalin group but surprisingly the intraoperative blood loss was not reduced. This is most probably returned to the different types of spine surgeries included in this study. Additionally, it was reported that pregabalin may induce thrombocytopenia although it was prominent mostly after 5 days of continuous utilization .
In this study, pregabalin was scheduled nearly 1 h before induction. This is because the peak plasma concentration of this drug after single oral administration occurs after about 1 h, with high bioavailability and predictable linear pharmacokinetics .
Lumbar discectomy is a common surgical procedure and is commonly followed by moderate-intensity postoperative pain . Our results showed apparent analgesia in the pregabalin group implicated by lower VAS and morphine consumption. Many studies have confirmed this effect using the same dose of pregabalin in similar spine surgeries ,.
Typically, postoperative pain is characteristically nociceptive which implicates the peripheral mechanoreceptor stimulation; besides, it is established that inflammatory, visceral, and neurogenic components also shears to the acute pain symptoms. It has been proposed that postoperative pain can be combined with a reversible brief variety of neuropathic pain . It was confirmed that mechanical hyperalgesia around the wound postoperatively contribute to the general mechanism involving central neuronal sensitization . This could explain the analgesic effect of pregabalin as it blocks both hyperalgesia and central sensitization .
In this current study, postoperative complications were comparable in both groups. This is in agreement with Jokela et al.  that 150 mg pregabalin is effective for postoperative analgesia without a significant increase in side effects such as dizziness, headache, nausea, vomiting, or pruritus. Also, in 22 patients who received 150 mg pregabalin administered 1 h before an elective lumbar single-level microdiscectomy the incidence of pruritus, nausea, vomiting, and dizziness were 0.05, 0.09, 0, and 0%, respectively .
However in a study of 90 patients who underwent abdominal hysterectomy after receiving 300 mg pregabalin, the incidence of somnolence was 40% in the pregabalin group and 3.3% in the control group, whereas 20% reported dizziness in the pregabalin group and 3% in the control group which may be related to doubling the dose of pregabalin .
Limitation of the study was the inclusion of different types, invasiveness, and duration of lumbar spinal surgeries.
| Conclusion|| |
Premedication with oral 150 mg pregabalin before elective spinal surgery in adults facilitated induced hypotension. Furthermore, it attenuated the stress response to tracheal intubation and provided postoperative analgesia.
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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]