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LETTER TO EDITOR
Year : 2014  |  Volume : 8  |  Issue : 5  |  Page : 115-116

Could pregabalin premedication predispose to perioperative atrial fibrillation in patients with sepsis?


Department of Anesthesiology and Critical Care, University College of Medical Sciences and Guru Teg Bahadur Hospital, Shahdara, New Delhi, India

Correspondence Address:
Dr. Rachna Wadhwa
Department of Anesthesiology and Critical Care, University College of Medical Sciences and Guru Teg Bahadur Hospital, Shahdara, New Delhi - 110 095
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-354X.144096

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Date of Web Publication6-Nov-2014
 


How to cite this article:
Chilkoti G, Wadhwa R, Saxena A, Khurana P. Could pregabalin premedication predispose to perioperative atrial fibrillation in patients with sepsis?. Saudi J Anaesth 2014;8, Suppl S1:115-6

How to cite this URL:
Chilkoti G, Wadhwa R, Saxena A, Khurana P. Could pregabalin premedication predispose to perioperative atrial fibrillation in patients with sepsis?. Saudi J Anaesth [serial online] 2014 [cited 2020 Feb 23];8, Suppl S1:115-6. Available from: http://www.saudija.org/text.asp?2014/8/5/115/144096

Sir,

Atrial fibrillation (AF) is a commonly encountered arrhythmia in the perioperative period in septic patients. [1] Pregabalin, an antiepileptic agent when used for providing pain relief in chronic pain is known to be associated with arrhythmias; [2] however, there have been no case report of arrhythmia associated with pregabalin premedication. We, hereby, hypothesize that pregabalin premedication in the septic patient may possibly contribute to the development of AF in the perioperative period.

A 45-year-old female patient, weighing 60 kg, American Society of Anesthesiologists Grade I, was rescheduled for right sided hemi-arthroplasty after having undergone two major elective surgeries. She had already undergone right sided hemi-arthroplasty 6 months back for subcapitate fracture of neck of femur. It was followed by infected implant for which patient again underwent second surgery for implant removal with insertion of antibiotic coated spacer and wound debridement within a month of the previous surgery. For both surgeries, regional anesthesia was administered and the perioperative period remained uneventful. Now, the patient was rescheduled for hemi-arthroplasty. This time patient was receiving antibiotics; injection teicoplanin and injection amikacin. All preoperative investigations were within normal range except for the markedly raised total leucocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She was advised capsule pregabalin 150 mg, night prior to surgery and again on the morning of surgery, 2 h prior to the scheduled surgery.

In the operation theater, routine monitoring was instituted, which showed noninvasive blood pressure of 100/70 mmHg with 99% SpO 2 . However, the continuous electrocardiogram (ECG) showed coarse AF with a heart rate (HR) of 150-160 beats/min and irregularly irregular rhythm. At this time, patient was drowsy, but arousable and responding to verbal commands. Patient denied any complaints of anxiety, headache, nausea, chest pain, palpitation or difficulty in breathing. Defibrillator and all resuscitative drugs and equipments were kept ready. Cardioversion was not considered as the patient did not have any signs of unstable tachyarrthymias. Injection metoprolol was administered to control ventricular rate in aliquots of 1 mg to a total of 3 mg. A 12-lead ECG with long strip of lead-II was done, cardiology opinion was sought and surgery was postponed. The cardiologist confirmed the diagnosis of AF on 12-lead ECG and advised amiodarone infusion and further cardiac evaluation. Systolic blood pressure (SBP) remained above 90 mmHg throughout this period. As the HR continued to remain refractory to beta-blockers, intravenous amiodarone 150 mg bolus was administered over a period of 10 min followed by infusion at 1 mg/min. HR reduced to 90/min and SBP increased to 120 mmHg. AF reverted to sinus rhythm within 20-25 min of starting amiodarone infusion. Arterial blood gas and serum electrolytes were within the normal limits. Thereafter, patient was shifted to intensive care unit (ICU) for observation and further management. In ICU, troponin T, creatine phosphokinase-myoglobin, serum electrolytes, and transthoracic echocardiography were done and found to be within normal limits. Cardiologist advised to continue amiodarone infusion at the rate of 1 mg/min for another 6 h and to start aspirin 75 mg once daily. Patient was transferred to ward after 24 h of observation in ICU. After 2 weeks, patient was again scheduled for right sided hemiarthroplasty and the sepsis biomarker (e.g., CRP) had started showing a decreasing trend by this time. Considering the predisposition for arrhythmia, pregabalin was not advised for premedication this time. The surgery was conducted successfully without any perioperative ECG changes.

On retrospective analysis, we speculate that AF is attributed to the combined effect of underlying sepsis and oral pregabalin premedication in our patient. Sepsis is known to be associated with arrhythmias. Myocardial dysfunction in sepsis is an important contributing factor inducing AF. [3] Dernellis and Panaretou, observed a direct association between the raised CRP and presence of AF, from a large cohort study of 5000 elderly individuals when followed for a mean of 6.9 years. [4] Our patient had underlying sepsis, which was authenticated by infected implant and raised levels of CRP and ESR.

Second, the other predisposing factor for development of AF could be co-administration of pregabalin premedication in our patient. Pregabalin, a gamma amino butyric acid analogue, is indicated for chronic neuropathic pain, and generalized anxiety disorder and is also very commonly used for premedication in anesthesia practice. Oral pregabalin premedication effectively leads to sedation and analgesia with successful attenuation of the adverse and deleterious hemodynamic pressor response. [5]

Cardiac events with pregabalin are rarely reported in literature. It is related to the binding of pregabalin to a2δ2 subunits of voltage gated calcium channel causing potassium-evoked accentuation of calcium influx in the heart. A French pharmacovigilance database have found the incidence of pregabalin suspected cardiac arrhythmia and conduction disturbances (e.g., bradycardia, tachycardia, AF, junctional arrhythmia) to be as high as 57% in patients on chronic pregabalin therapy for chronic pain relief. [6] To the best of our knowledge, arrhythmia has never been reported as an adverse event with oral pregabalin premedication.

The oral bioavailability of pregabalin is estimated to be 90% and is not bound to plasma proteins. The steady state concentration is achieved within 24-48 h. An important pharmacokinetic characteristic of pregabalin is that it is absorbed rapidly when administered in the fasted state, with peak concentration occurring within 1 h following both single and multiple doses. [6] Our patient received the morning dose of pregabalin 150 mg in fasted state just 2 h before shifting to operation theater, when patient was diagnosed to have AF.

We conclude that pregabalin premedication in a septic patient may contribute to arrhythmia in the perioperative period. Thus, it may be warranted to avoid pregabalin premedication in patients who are known or suspected to have underlying sepsis.

 
  References Top

1.
Ankichetty S, Nandhakumar A, Subramanyam R, Venkatraghavan L. Acute atrial fibrillation in emergency surgery: Is it rare? Indian J Anaesth 2011;55:287-9.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Fuzier R, Serres I, Guitton E, Lapeyre-Mestre M, Montastruc JL, French Network of Pharmacovigilance Centres. Adverse drug reactions to gabapentin and pregabalin: A review of the French pharmacovigilance database. Drug Saf 2013;36:55-62.  Back to cited text no. 2
    
3.
Goss CH, Carson SS. Is severe sepsis associated with new-onset atrial fibrillation and stroke? JAMA 2011;306:2264-6.  Back to cited text no. 3
[PUBMED]    
4.
Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. Eur Heart J 2004;25:1100-7.  Back to cited text no. 4
    
5.
Gupta K, Bansal P, Gupta PK, Singh YP. Pregabalin premedication - A new treatment option for hemodynamic stability during general anesthesia: A prospective study. Anaesth Essays Res 2011;5:57-62.  Back to cited text no. 5
    
6.
Martinez L, Therasse C, Ginisty S, Eftekhari P. Cardiac events and pregabalin: Spontaneous Reports Notified to the French Pharmacovigilance Database. Abstract Presented at VIII EME Centre de Congres D Angers 22-24 April 2013, France.  Back to cited text no. 6
    




 

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