Preoperative Low-dose and High-dose Pregabalin and Cardiovascular Response to Endotracheal Intubation: A Prospective, Randomized, Single-blind, Controlled Study in China

Chen, Wei; Huang, Huiyun; Chuanxin, Yang; Hu, Xiaoqing; Bao, Fang; Jiang, Hui

doi:10.1016/j.clinthera.2018.11.006

Cited by 7 publications

(7 citation statements)

References 34 publications

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“…We also found that patients receiving either pregabalin or diazepam had higher sedation scores in comparison to placebo. This finding was consistent with previous studies [43][44][45][46] . However, there were no serious adverse events associated with either treatment, such as respiratory depression or hemodynamic disturbance occurred in either group.…”

Section: Discussionsupporting

confidence: 94%

The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo

Nimmaanrat,

Charuenporn,

Jensen

et al. 2023

Sci Rep

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We aimed to evaluate the potential anxiolytic effects of premedication with pregabalin, compared with diazepam and placebo. We conducted this non-inferiority, double-blind, randomized controlled trial in ASA classification I-II patients aged 18–70 years, scheduled for elective surgery under general anesthesia. They were allocated to receive pregabalin (75 mg the night before surgery and 150 mg 2 h before surgery), diazepam (5 and 10 mg in the same manner) or placebo. Preoperative anxiety was evaluated using verbal numerical rating scale (VNRS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) before and after premedication. Sleep quality, sedation level, and adverse effects were assessed as secondary outcomes. A total of 231 patients were screened and 224 completed the trial. The mean change (95%CI) in anxiety scores from before to after medication in pregabalin, diazepam, and placebo groups for VNRS were − 0.87 (− 1.43, − 0.30), − 1.17 (− 1.74, − 0.60), and − 0.99 (− 1.56, − 0.41), and for APAIS were − 0.38 (− 1.04, 0.28), − 0.83 (− 1.49, − 0.16), and − 0.27 (− 0.95, 0.40). The difference in change for pregabalin versus diazepam was 0.30 (− 0.50, 1.11) for VNRS and 0.45 (− 0.49, 1.38) for APAIS, exceeding the limit of inferiority for APAIS of 1.3. Sleep quality was statistically different between pregabalin and placebo groups (p = 0.048). Sedation in pregabalin and diazepam groups were significantly higher than placebo group (p = 0.008). No significant differences of other side effects, except dry mouth was higher in placebo group compared with diazepam (p = 0.006). The study filed to provide evidence at non-inferiority of pregabalin compared to diazepam. Furthermore, premedication with either pregabalin or diazepam did not significantly reduce the preoperative anxiety in comparison to placebo, despite the fact that both resulted in higher levels of sedation. Clinicians should weigh the benefits and risks of premedication with these 2 drugs.Thai Clinical Trials Registry: TCTR20190424001 (24/04/2019) Registry URL: https://www.thaiclinicaltrials.org/.

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Section: Discussionsupporting

confidence: 94%

The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo

Nimmaanrat,

Charuenporn,

Jensen

et al. 2023

Sci Rep

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“…This notion is supported by our findings that memantine and gabapentin, two clinically used drugs that inhibit NMDARs and a2d -1, respectively, similarly reversed CUMS-induced persistent hypertension in BHR. Clinical studies show that both memantine and gabapentin reduce anxiety (Lavigne et al, 2012;Schwartz et al, 2012) and that gabapentinoids attenuate tracheal intubation-induced pressor responses (Fassoulaki et al, 2006;W. Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

α2δ-1–Dependent NMDA Receptor Activity in the Hypothalamus Is an Effector of Genetic-Environment Interactions That Drive Persistent Hypertension

et al. 2021

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The interplay between genetic and environmental factors is critically involved in hypertension development. The paraventricular nucleus (PVN) of the hypothalamus regulates sympathetic output during stress responses and chronic hypertension. In this study, we determined mechanisms of synaptic plasticity in the PVN in chronic stress-induced persistent hypertension in male borderline hypertensive rats (BHR), the first offspring of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In Wistar-Kyoto rats, chronic unpredictable mild stress (CUMS) increased arterial blood pressure (ABP) and heart rate, which quickly returned to baseline after CUMS ended. In contrast, in BHR, CUMS caused persistent elevation in ABP, which lasted at least 2 weeks after CUMS ended. CUMS also increased the mRNA level of a2d-1 and synaptic protein levels of GluN1, a2d-1, and a2d-1-GluN1 complexes in the PVN in BHR. Furthermore, CUMS significantly increased the frequency of miniature EPSCs and the amplitude of NMDAR currents in spinally projecting PVN neurons in BHR; these increases were normalized by blocking NMDARs with AP5, inhibiting a2d-1 with gabapentin, or disrupting the a2d-1-NMDAR interaction with a2d-1Tat peptide. Microinjection of AP5 or a2d-1Tat peptide into the PVN normalized elevated ABP and renal sympathetic nerve activity in stressed BHR. In addition, systemically administered gabapentin or memantine attenuated higher ABP induced by CUMS in BHR. Our findings indicate that chronic stress-induced persistent hypertension is mediated by augmented sympathetic outflow via a2d-1-bound NMDARs in the PVN. This new information provides a cellular and molecular basis for how the genetic-environment interactions cause persistent hypertension.

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“…As can be seen from Table 2 , non-significant results of hemodynamic parameters were in disagreement with results that pain scores at 2 h showed significant differences. One reasonable explanation is that although hemodynamic parameters could reflect the change of pain, they are also considered susceptible to other factors such as analgesic medications (including paracetamol, opioids, and non-steroidal anti-inflammatory drugs) [ 37 , 49 , 50 , 51 ]. Hence, analgesic medications such as opioids inducing hypotension may mask hemodynamic parameter changes induced by pain.…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

Wang

Dong

et al. 2023

Medicina

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Background and Objectives: As an adjunct to postoperative multimodal analgesic regimens, pregabalin has been reported in reducing postoperative acute pain and opioid consumption. However, there is only a small amount of evidence for preemptive pregabalin in patients undergoing cancer-related surgery. This systematic review was conducted to integrate high-quality evidence to evaluate the preemptive analgesic effects of pregabalin in cancer-related surgery. Materials and Methods: Seven electronic databases were searched in a combination of subject terms and free words. Efficacy and safety of preemptive pregabalin on postoperative pain for cancer-related surgery were evaluated by assessing resting and dynamic pain scores postoperatively, cumulative morphine equivalent consumption, time to first analgesic request, hemodynamic parameters, and the safety indicators. Results: Thirteen trials were incorporated for quantitative synthesis. The pooled results showed administration of pregabalin preoperatively is clinically significant for improving resting (weighted mean difference (WMD), −1.53 cm; 95% CI, −2.30 to −0.77) and dynamic (WMD, −1.16 cm; 95% CI, −2.22 to −0.11) pain severity scores at 2 h postoperatively and prolonging time to first analgesic request (WMD, 2.28 h; 95% CI, 0.79 to 3.77) in cancer-related surgery. Preemptive pregabalin was also statistically effective in some other pain indicators but would increase the risk of pregabalin-related side effects after surgery. Conclusions: Our findings do not support the administration of pregabalin in doses larger than 300 mg when put in cancer-related surgery. Taken together, more high-quality research particularly focused on the optimal dosages and timing of pregabalin in cancer-related surgery is needed in the future to establish stronger evidence for therapeutic effects.

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Preoperative Low-dose and High-dose Pregabalin and Cardiovascular Response to Endotracheal Intubation: A Prospective, Randomized, Single-blind, Controlled Study in China

Cited by 7 publications

References 34 publications

The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo

The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo

α2δ-1–Dependent NMDA Receptor Activity in the Hypothalamus Is an Effector of Genetic-Environment Interactions That Drive Persistent Hypertension

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

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