Naveen Eipe

A protocol for a systematic review for perioperative pregabalin use

BackgroundPerioperative pain management has recently been revolutionized with the recognition of novel mechanisms and introduction of newer drugs. Many randomized trials have studied the use of the gabapentinoid anti-epileptic, pregabalin, in acute pain. Published systematic reviews suggest that using pregabalin for perioperative pain management may decrease analgesic requirements and pain scores, at the expense of troublesome side effects. A major limitation of the extant reviews is the lack of rigorous investigation of clinical characteristics that would maximize the benefit harms ratio in favor of surgical patients. We posit that effects of pregabalin for perioperative pain management vary by the type of surgical pain model and propose this systematic review protocol to update previous systematic reviews and investigate the heterogeneity in findings across subgroups of surgical pain models.Methods/DesignUsing a peer-reviewed search strategy, we will search key databases for clinical trials on perioperative pregabalin use in adults. The electronic searches will be supplemented by scanning the reference lists of included studies. No limits of language, country or year will be imposed. Outcomes will include pain; use of co-analgesia, particularly opioids; enhanced recovery; and drug-related harms. We will focus on the identification of surgical models and patient characteristics that have shown benefit and adverse effects from pregabalin.Two clinical experts will independently screen the studies for inclusion using eligibility criteria established a priori. Data extracted by the reviewers will then be verified. Publication bias will be assessed, as will risk of bias using the Cochrane Risk of Bias tool. Meta-analysis and meta-regression are planned if the studies are deemed statistically, methodologically and clinically homogenous. Evidence will be graded for its strength for a select number of outcomes.DiscussionWe will explore the findings of perioperative clinical trials studying the use of pregabalin for acute pain. We will comment on the implications of the findings and provide further direction for the appropriate use of pregabalin in acute pain. This protocol will attempt to bridge the growing gap between clinical experience and emerging evidence, and has the potential to aid future guideline development in the perioperative use of pregabalin.Systematic review registrationPROSPERO registration number CRD42012002078

Ultra-low-dose ketamine infusion for ischemic limb pain

To the Editor, Ketamine is widely used in acute pain management and has found special application in patients with opioid tolerance, acute hyperalgesia, and chronic neuropathic pain. We report the pain management of a patient with ischemic limb pain using an ultra-low-dose ketamine infusion. A 40-yr-old male (80 kg, American Society of Anesthesiologists’ physical status IV) with a complex medical history (diabetes mellitus type 2, diabetic neuropathy, end-stage renal disease on peritoneal dialysis, peripheral vascular disease, and hypertension) presented with worsening ischemia of his right leg. Initially, he underwent below-knee amputation under epidural anesthesia, and the epidural was continued for analgesia for three days after surgery. After the epidural was discontinued, oral multimodal analgesia with acetaminophen (650 mg po q4h), pregabalin (50 mg po q am), tramadol (25 mg po q12h), and nortriptyline (10 mg po qhs). In addition, he was prescribed intermittent doses of hydromorphone (0.5 mg sc or 1-2 mg po q4h prn) for breakthrough pain. The patient appeared to be very sensitive to these small doses of opioids he complained of nausea, vomiting, sedation, and hallucinations. These side effects limited the amount of opioid that could be used, and his pain continued to be inadequately controlled. He remained in hospital for another three weeks with worsening pain due to poor healing of the stump. The patient’s pain became difficult to control and he refused any opioid analgesia. At this point, the surgeons reconsulted the Acute Pain Service (APS). On evaluation, the patient reported a pain score (numerical rating score 0-10) of 8/10 at rest and 12/10 with movement. In addition to phantom pain and allodynia, he described pain in the amputated leg as shooting, sharp, and thunder-like. After careful discussion, the APS physician administered a small ‘‘test’’ dose of ketamine (2 mg iv q 15 min, 6 mg total). The pain decreased dramatically to 4/10 without any psychomimetic side effects. A decision was made to stop the intermittent opioids and to start a ketamine infusion at 1.5-5 mg hr. Three days after initiating the ketamine infusion, the surgeons decided to proceed with above-knee amputation due to persistent stump ischemia and infection. Surgery was done under general anesthesia supplemented with a single-shot femoral nerve block. Postoperatively, opioids were not prescribed and the ketamine infusion was re-initiated. The ketamine infusion was titrated to provide analgesia (within the range of 1-5 mg hr) and continued for four days. Daily ketamine requirement and pain scores are shown in the Figure. The patient was discharged home after one week with minimal pain and no side effects from the ketamine. He continued to take pregabalin (25 mg bid) and tramadol (25 mg prn) with consistent pain scores of 3/10 at rest and 5/10 with activity. He remained well at follow-up six months after his amputation and returned to the operating room for an uneventful revascularization of his other leg. The effective treatment of ischemic limb pain remains a clinical and pharmacological challenge. There is evidence suggesting that neuropathic mechanisms play a major role in this type of pain due to ischemia or direct damage to the nerve. One other explanation for neuropathic pain may be the N-methyl-D-aspartate receptor-mediated increases in synaptic excitability of the spinal cord, clinically manifested as hyperalgesia and allodynia. Ischemic limb Q. A. Tawfic, MBChB N. Eipe, MD (&) J. Penning, MD Department of Anesthesiology, The Ottawa Hospital, Ottawa, ON, Canada e-mail: neipe@toh.on.ca

Assessing the feasibility of a randomised, double-blinded, placebo-controlled trial to investigate the role of intraperitoneal ropivacaine in gastric bypass surgery: a protocol

Introduction Postoperative pain control remains a major challenge for surgical procedures, including laparoscopic gastric bypass. Pain management is particularly relevant in obese patients who experience a higher number of cardiovascular and pulmonary events. Effective pain management may reduce their risk of serious postoperative complication, such as deep vein thrombosis and pulmonary emboli. The objective of this study is to evaluate the efficacy of intraperitoneal local anaesthetic, ropivacaine, to reduce postoperative pain in patients undergoing laparoscopic Roux-en-Y gastric bypass. Methods and analysis A randomised controlled trial will be conducted to compare intraperitoneal ropivacaine (intervention) versus normal saline (placebo) in 120 adult patients undergoing bariatric bypass surgery. Ropivacaine will be infused over the oesophageal hiatus and throughout the abdomen. Patients in the control arm will undergo the same treatment with normal saline. The primary end point will be postoperative pain at 1, 2 and 4 h postoperatively. Pain measurements will then occur every 4 h for 24 h and every 8 h until discharge. Secondary end points will include opioid use, peak expiratory flow, 6 min walk distance and quality of life assessed in the immediate postoperative period. Intention-to-treat analysis will be used and repeated measures will be analysed using mixed modelling approach. Post-hoc pairwise comparison of the treatment groups at different time points will be carried out using multiple comparisons with adjustment to the type 1 error. Results of the study will inform the feasibility of recruitment and inform sample size of a larger definitive randomised trial to evaluate the effectiveness of intraperitoneal ropivacaine. Ethics and dissemination This study has been approved by the Ottawa Health Science Network Research Ethics Board and Health Canada in April 2014. The findings of the study will be disseminated through national and international conferences and peer-reviewed journals. Trial registration number Clinicaltrial.gov NCT02154763.

Airway management in cervical spine ankylosing spondylitis: Between a rock and a hard place

We report the perioperative course of a patient with long standing ankylosing spondylitis with severe dysphagia due to large anterior cervical syndesmophytes at the level of the epiglottis. He was scheduled to undergo anterior cervical decompression and the surgical approach possibly precluded an elective pre-operative tracheostomy. We performed a modified awake fibreoptic nasal intubation through a split nasopharyngeal airway while adequate oxygenation was ensured through a modified nasal trumpet inserted in the other nares. We discuss the role of nasal intubations and the use of both the modified nasopharyngeal airways we used to facilitate tracheal intubation. This modified nasal fibreoptic intubation technique could find the application in other patients with cervical spine abnormalities and in other anticipated difficult airways.

“CAPS” Cardiac Acute Pain Services—A Nationwide Survey From Canada

OBJECTIVES Acute Pain Services (APS) are well-established worldwide; however, their availability and use in cardiac surgery units are less widespread and, even where present, may be provided less consistently. The authors undertook this survey to assess the current organization of Cardiac Acute Pain Services (CAPS) in Canada. DESIGN This was a prospectively administered survey. SETTING This study included all centers in Canada that conducted adult cardiac surgery. PARTICIPANTS The participants were anesthesiologists. INTERVENTION A 20-item questionnaire covered the demographics, functioning and APS structure. RESULTS The authors achieved a response rate of 100% with completed questionnaires from all 31 centers. Ten centers (32.3%) stated that they had a dedicated CAPS, 9 centers (29%) stated that they did not have an APS, and 12 centers (38.7%) had APS but no CAPS. At the time of the survey for the 10 centers with CAPS, 3 of the CAPS had a physician-run model, 4 had a combined physician and nurse service, and 1 used a combination of protocols, intensivists, and nurse practitioners. Nine centers had an anesthesiologist assigned to daily acute pain rounds. Only in 2 of 10 centers with CAPS were more than 50% of their cardiac surgery patients receiving care. In general, postoperative pain management was a protocol-driven activity. CONCLUSIONS CAPS are varied in both structure and functioning. Further work is required both at the institutional and the national levels to improve the postoperative care and the pain-related outcomes of patients undergoing cardiac surgery.

Opioid conversions and patient-controlled analgesia parameters in opioid-dependent patients

To the Editor, While a recent Continuing Professional Development article outlined the perioperative management of patients taking opioids for chronic pain, others have highlighted the serious consequences of opioid use in these patients. Patients who need opioids for pain prior to their surgery almost always require these to be continued throughout the perioperative period. ‘‘Conversion’’ tables have been developed to calculate the parenteral equivalent of oral opioids. The conventional conversion ratio between oral and intravenous routes for morphine or hydromorphone is considered to be threefold (3:1); however, for patients on long-term or escalating doses of opioids, multiple conversion ratios have also been advocated. Due to the uncertainty regarding the exact conversion ratio in the individual patient, we suggest that it is best to assume that the oral to intravenous ratio is high when converting extended-release oral tablets to intravenous opioids. On the contrary, it is safer to use a low intravenous to oral ratio when converting from intravenous opioids to oral tablets. To estimate the new dose, we recommend that two different ratios be used depending on the ‘‘direction’’ of conversion, i.e., 4:1 for oral to intravenous and 1:2 for intravenous to oral, as shown in the Dual Ratio Opioid Conversion Chart we have developed to manage acute pain in opioid dependent patients (Figure). These dual ratios provide a conservative estimate for a new opioid dose, and depending on the direction of conversion, they provide a 25% or 33% reduction when compared with the conventional threefold ratio. The second challenge in opioid-dependent patients requiring patient-controlled analgesia (PCA) is to set appropriate parameters. For those who are unable to take oral opioids in the perioperative period, we add a basal infusion for half the hourly intravenous equivalent (Figure). During the stable maintenance phase for effective analgesia, patients should not require more than two PCA boluses per hour on average. This appropriate bolus-demand frequency is dependent upon an appropriately chosen bolus size. To determine the PCA bolus size in opioid-dependent patients, the opioid dose-response should be compared with that of an opioid-naive patient in whom the standard morphine PCA bolus size is 1 mg. The magnitude of the shift of the opioid dose-response curve is calculated by dividing the daily oral morphine equivalent by 100 mg and multiplying the standard bolus size (1 mg of morphine) by this factor. For example, a patient taking 400 mg per day of oral morphine preoperatively has approximately a fourfold (400/100 = 4) increase in opioid requirement and would require a 4 mg PCA bolus dose. For such a patient, the starting PCA settings would be a 4 mg bolus, a basal infusion rate of 2 mg hr, a lockout interval of six minutes, and an hourly limit of 32 mg. At the end of the perioperative phase, if this patient requires 100 mg of intravenous morphine per day for adequate analgesia, we would recommend 200 mg of oral morphine in divided doses for oral use based on the Dual Ratio Opioid Conversion Chart. Richebe et al. suggested setting the continuous (basal) infusion equivalent to the total preoperative opioid use and keeping the bolus dose unchanged. Previously, Hadi et al. suggested setting half of the preoperative dose as the basal and increasing the bolus dose by 50%. Both of these This work should be attributed to the Department of Anesthesiology, The Ottawa Hospital, Ottawa.

Initial experience with dexmedetomidine for acute pain crises

To the Editor, Dexmedetomidine is a centrally acting alpha-2 adrenergic agonist approved for procedural sedation and for sedation in intensive care unit (ICU) patients for up to 24 hr. We report the use of dexmedetomidine for managing acute postoperative pain in two patients. A 35-yr-old man was admitted to a Level 1 trauma centre following a traffic accident with a compound crush injury to his right leg. Initial presentation was complicated by wound infection, sepsis, and rhabdomyolysis that required surgical management, eventually leading to above-knee amputation. The Acute Pain Service (APS) was consulted for pain management. As the APS suggested, we initiated intravenous hydromorphone with a patient-controlled analgesia device and an oral multimodal analgesia protocol that included acetaminophen, celecoxib, tramadol, and pregabalin. The patient then underwent five surgeries over ten days. On postoperative day 12, he began to experience recurrent acute pain crises. Despite maximizing the multimodal oral therapy, escalating parenteral opioids, and adding intravenous ketamine and lidocaine, the pain control was unsatisfactory. Because regional anesthesia was still relatively contraindicated due to his recent sepsis and rhabdomyolysis, a trial of dexmedetomidine was considered. In the fully monitored Trauma Unit, he was given dexmedetomidine (1 lg kg bolus over 20 min), after which his pain score decreased from 10/10 to 4/10. An infusion of dexmedetomidine was then started (0.4 lg kg hr) and continued for 48 hr. The next day, oral clonidine was initiated, with the dose gradually increased over the next two days (maximum 0.2 mg po q8h) as he was being weaned from the dexmedetomidine. For his next (final) surgery, he had a lumbar epidural which remained in place for four days. After it was discontinued, the recurrent pain crises resumed, and he was unable to tolerate any dressing or position changes. Dexmedetomidine was restarted and continued for another three days with continuous monitoring (range 0.1-0.4 lg kg hr). Pain scores and opioid requirements gradually decreased. The dexmedetomidine infusion was titrated down and discontinued as the pain control stabilized. He was discharged to a rehabilitation institution with multimodal oral analgesics. The second patient was a 70-yr-old woman with chronic pain secondary to severe rheumatoid arthritis who was scheduled to undergo revision occipitocervical fusion. Her baseline pain scores, on average, were 8/10 with an analgesic regimen that included acetaminophen, meloxicam, tramadol, oxycodone, pregabalin, memantine, methadone, and subcutaneous fentanyl infusion via a continuous ambulatory pump. Immediately after the spine surgery, she was transferred to the ICU (intubated and sedated) for postoperative ventilation and pain control. The APS orders included infusions of ketamine (20 mg hr) Presented in part as an Abstract at the CAS Annual Meeting (2016, Vancouver) and the World Congress of Anesthesiology (2016, Hong Kong).

Submental intubation: another anesthetic option for maxillofacial trauma

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An unusual case of hemolysis

To the Editor: A 55-yr-old ASA I miner presented with chronic arthritis of the left hip with failed implant in situ and non-union of the fractured neck of the femur. He had undergone two previous surgeries performed elsewhere with no available documents. From the patient’s account, they were uneventful and he did not require any transfusion of blood. He was admitted in our institution for a total hip replacement. Clinical examination was unremarkable except for the stiff and painful left hip. His preoperative investigations were normal with hemoglobin of 120 g·L–1. Perioperative blood transfusion was anticipated and a blood sample for cross-match was sent. The blood bank technologist reported that the sample had hemolyzed. Another sample, sent on the day of surgery was also reported to have hemolyzed. The surgery was postponed, until further tests were performed to rule out any underlying serious hematological condition that was causing the hemolysis of the samples. The laboratory tests revealed a normal peripheral blood smear. The reticulocyte, total and differential leukocyte counts were normal. The bleeding time, prothrombin time, activated partial thromboplastin time; thrombin time and the D-dimer were within normal limits. The liver and renal function tests did not show any abnormality. These tests ruled out the common bleeding and clotting abnormalities. Another cross-match sample was sent in a similar reusable bottle, which did not exhibit any evidence of hemolysis. The patient underwent surgery, which was uneventful and did not warrant any transfusion. Hemolysis of cross-match and other clotted blood samples commonly occurs in the presence of disseminated intravascular coagulation and drug-induced hemolysis. In many developing countries cross-match and other blood samples are collected in reusable bottles. A review of the case pointed towards the possibility of contamination of the reusable bottles in which the cross-match sample was collected, since two other incidents were reported in the hospital on the same day. Contaminants such as detergent are likely to have been the cause in this case. The mechanism by which detergents cause hemolysis has been described.1 Careful screening of reusable bottles and strict quality control measures could prevent this from occurring. Nevertheless, this case highlights the need for vigilance and investigation into incidents when crossmatch or other clotted blood samples undergo spontaneous hemolysis. This may indicate serious underlying condition, which would require appropriate perioperative blood component therapy2 and modification of anesthetic technique.3