Ketamine for pain relief in acute pancreatitis

Acute Pain (2007) 9, 83—86 SHORT COMMUNICATION Ketamine for pain relief in acute pancreatitis Mahesh Chaudhari a,∗, Shefali Chaudhari a, S. Mather b a b University Hospitals Coventry and Warckshire, Clifford Bridge Road, Coventry CV2 2DX, UK South Wawickshire Hospitals NHS Trust, Lakin Road, Warwick CV34 5BW, UK Received 23 October 2006 ; received in revised form 2 April 2007; accepted 3 April 2007 KEYWORDS Ketamine; Acute pancreatitis; Pain Summary Patients with acute pancreatitis are often admitted to critical care unit and present with a spectrum of multiorgan problems. The commonest presenting symptom of acute pancreatitis is upper abdominal pain. The pain can be very severe and refractory to the treatment with conventional analgesics. The pain not only adds to the patient’s distress but may also have adverse effects on the cardio-respiratory systems, which can be affected by acute pancreatitis itself. The pain in acute pancreatits is usually controlled by conventional analgesics, morphine/pethidine PCA or epidural analgesia. But at times all these measures of pain control fail and additional methods of pain relief become necessary. We encountered a patient with acute pancreatits with severe abdominal pain in whom conventional methods of pain relief failed to provide adequate analgesia. The patient had respiratory impairment secondary to upper abdominal pain and improved pain relief avoided the possible need for invasive ventilation. We used an intravenous ketamine infusion to supplement the analgesic regimen with a significant improvement in pain relief without any adverse psycho mimetic effects. The probable mechanisms of action of ketamine in improving pain relief are discussed. On search of the literature, the use of ketamine for pain relief in acute pancreatitis has never been reported. © 2007 Elsevier B.V. All rights reserved. 1. Case report A 56-year-old 70-kg female patient was admitted to the surgical ward with an acute onset of upper abdominal pain and vomiting. Based on the history and clinical examination a provisional diagnosis of acute pancreatitis was ∗ Corresponding author at: 4 Rowthorn Drive, Solihull, West Midlands B90 4ST, UK. Tel.: +44 1217333757. E-mail address: shefnish@hotmail.com (M. Chaudhari). made. This diagnosis was confirmed by raised amylase and the abdominal CT scan which showed an inflamed pancreas with a necrotic portion in the head of the pancreas. There was neither a history of any recent viral infection, alcohol abuse, trauma nor a suggestion of medication ingestion (e.g. steroids, sulphonamides and azathioprines) that would cause pancreatitis. Her blood investigation results excluded hypercalcaemia or hyperlipidaemia. An ultrasound examination of the biliary tree did not show any gallstones. This suggested 1366-0071/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.acpain.2007.04.001 84 the cause of the pancreatitis was more likely to be idiopathic. She was known a non-insulin dependent diabetic and her only routine medication was oral hypoglycaemic drug. On admission her main problem was pain (VAS 3/10) in the upper abdomen, which was radiating to the back. Initially her pain responded to a conventional analgesic regimen (paracetamol and intermittent morphine injections). Pain was assessed and recorded using the visual analogue scale (VAS, 0 = no pain; 10 = worst possible pain). The patient’s oxygen saturation was 96% on oxygen 2 L/min. She was haemodynamically stable and had a good urine output. The severity of pain (VAS 9/10) gradually increased over the next 12 h following admission to the ward. Her morphine requirements slowly increased up to a maximum of 10 mg/h. The abdominal pain and distension started to adversely affect her ventilation. Her arterial blood gas results showed hypoxic respiratory failure. A chest X-ray showed bilateral basal atelectasis and small amount of bilateral pleural effusions. She required oxygen 10 L/min (by mask) to maintain adequate oxygenation. Her persistent, refractory abdominal pain and respiratory distress warranted involvement of the critical care team and was transferred to high dependency unit (HDU). On HDU, respiratory support in the form of CPAP was started. A lower thoracic epidural was sited to provide analgesia. After a bolus dose, epidural analgesia with an infusion of 0.1% bupivacaine with 2 ␮g/mL fentanyl/mL was commenced. This improved her pain relief (VAS 1/10). Satisfactory pain relief, physiotherapy and CPAP improved her ventilation and oxygenation. Over the next few hours her urine output deteriorated. CVP guided fluid resuscitation was done to successfully improve her urine output. Epidural analgesia provided adequate pain relief for the next 4 days but then on 5th day she started to have breakthrough pain (VAS 5/10), requiring administration of epidural boluses of higher strength local anaesthetic solution with opioids. Episodic pain initially responded to bolus doses but over a period of 24 h her pain (VAS 6/10) became more continuous. The epidural catheter was re-sited to rule out any displacement and to address an intermittent ‘blockage’ alarm by the infusion pump. Unfortunately, this did not improve her pain relief. The continuous abdominal pain affected her ventilation and thereby increased her level of CPAP requirement. Further chest X-ray showed increase in bilateral basal M. Chaudhari et al. collapse of lungs without change in previously noted small amount of bilateral pleural effusion. There was no evidence of pulmonary oedema on clinical examination or on chest X-ray. Her haemodynamic parameters remained within normal limits. The acute pain team was consulted with regards to refractory abdominal pain. The acute pain team advised the use of morphine PCA with only local anaesthetic solution via the epidural catheter. This regime did relieve her pain but only for a brief period of time. Thereafter pethidine PCA, fentanyl patches/infusion in combination with epidural local anaesthetic solutions were tried with transient periods of improved pain relief. The acute pain team then suggested using an intravenous ketamine infusion along with epidural bupivacaine and IV morphine infusion. They did consider a coeliac plexus and splanchnic nerve block but the potential risk of infection precluded this form of pain relief. An intravenous infusion of ketamine at rate of 10 mg/h was started along with epidural bupivacaine and IV morphine. This improved the pain relief (VAS 1/10) dramatically within 2—3 h. The pain relief was sustained over initial 2 days but it became necessary to increase the infusion rate of ketamine up to 20 mg/h to maintain the adequate pain relief on day 3 onwards. Her morphine requirements slowly decreased after starting ketamine. The patient reported visual hallucinations (‘seeing kangaroos’) at some point on the 3rd day of starting the ketamine infusion, but no other adverse psycho mimetic side effects were reported. She did not have significant tachycardia or hypertension following ketamine infusion. With improved pain relief, the CPAP requirement steadily decreased. In the meantime, she was transferred to the regional liver unit for further management. Her cardiovascular and renal parameters remained stable over the entire period of admission without needing advanced form of support. Gradually, over a period of a week, her acute pancreatitis started to resolve. She did not undergo any surgical intervention. She was eventually discharged home. 2. Discussion The severe refractory abdominal pain associated with acute pancreatitis was treated with ketamine infusion in combination with opioids and epidural analgesia. Ketamine for pain relief in acute pancreatitis Ketamine has been used as adjuvant analgesic by SC, IV, epidural and intrathecal routes. It is shown to be effective in reducing the opioid requirements and related side effects [1—3]. Initially, our patient’s pain responded well to epidural analgesia but after 4 days pain intensity gradually increased. Despite increasing the doses of opioids and using various opioid drugs, both epidurally and intravenously, pain intensity remained intolerable. This could have been due to development of tolerance to epidural local anaesthetic solution and opioid. Use of ketamine, with epidural bupivacaine and morphine infusion, improved pain relief dramatically within few hours. This could have been due to two mechanisms. First, ketamine itself is a strong analgesic and second, could be due to reversal opioid tolerance and thereby increased the effectiveness of morphine. Ketamine is a potent analgesic at sub-anaesthetic doses by virtue of its action on NMDA receptors. Additionally, ketamine also reverse the opioid tolerance and thereby increases the effectiveness of opoids [4—6]. The blockade of NMDA receptors reduces or reverses opioid tolerance at spinal level. There is increasing body of evidence that suggest NMDA receptors are present in peripheral afferent nerves. In animal models, the interplay between peripheral opioid tolerance and existence of peripheral NMDA receptors has been demonstrated [7—9]. This model has also been demonstrated by Leung et al. [10]. In our patient, ketamine might have reversed the peripheral opioid tolerance as well and therefore increased the effectiveness of morphine peripherally. As ketamine provided effective pain relief without affecting consciousness, it was possible to use CPAP and chest physiotherapy effectively. These measures helped to maintain adequate ventilation and oxygenation. Without the adjuvant analgesic effect of ketamine, we would have, reluctantly, increased the dose of morphine infusion. This potentially could have had detrimental effect on ventilation with likely need for invasive ventilation. Use of ketamine probably avoided the requirement for invasive ventilation and potential complication associated with it. Adverse effects of ketamine are reported in previous case studies with dose of, usually, more than 500 mg/24 h [11]. In our patient, we used ketamine in dose of 240 mg/24 h on first 2 days and subsequently needed to increase to a maximum of 480 mg/24 h. Our patient did not have significant effect on cardiovascular parameters. 85 The patient reported to have seen ‘kangaroos’ with higher dose, which was not particularly distressing. Absence of significant adverse psycho mimetic effect in our patient could be due to smaller dose of ketamine used. In addition, the sedative effect of simultaneously used morphine might have had some antagonising effect on psycho mimetic side effects of ketamine. In summary, our case concludes that ketamine can be effectively used as an adjuvant analgesic with opioids to treat refractory pain in acute pancreatitis in critical care set up. Ketamine can also be used in patients developing tolerance to opioids or suffering from intolerable side effects of opioids in acute pain conditions. Conflict of interest We, all authors, do not have any conflict of interest in any part of the article. References [1] McQueen AL, Baroletti SA. Adjuvant ketamine analgesia for the management of cancer pain. Ann Pharmacother 2002;36:1614—9. [2] Wong CS, Shen TT, Liaw WJ, Cherng CH, Ho ST. Epidural coadministration of ketamine, morphine and bupivacaine attenuates post-herpatic neuralgia — a case report. 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