Comparative Evaluation of Clonidine as an Adjunct to Ropivacaine for Caudal Block Anaesthesia in Children Undergoing Sub-Umbilical Surgeries

BACKGROUND Studies suggest that clonidine can improve the duration of analgesia, quality of pain control when used with ropivacaine for caudal blocks in children. This study was designed to understand the effects of caudally administered ropivacaine 0.25 % (1ml/kg) alone and ropivacaine 0.25 % (1ml/kg) with clonidine 2 mcg/kg, in children between 2- 10 years. METHODS Sixty children posted for various sub-umbilical surgical procedures were included after written informed consent and ethics committee approval. Children were randomly divided into 2 groups of 30 each: Group R —ropivacaine 0.25 % 1 ml/kg into caudal epidural space and Group RC—ropivacaine 0.25 % 1 ml/kg and clonidine 2 mcg/kg into caudal epidural space. RESULTS The mean age of patients was similar with no statistical difference (4.83 vs 5.36, P = 0.3353). The duration of anaesthesia was significantly longer in the RC group (544.83 minutes vs 268.00 minutes, P < 0.0001). The effect size was very high (Cohen d=23.86). The pain score was comparable up to 1 hour for the two groups. But 2 hours later, the pain scores were significantly lower for the ropivacaine and clonidine groups. The effect on motor blockade was similar in both groups with no motor blockade at 4 hours follow up. 5 cases of urinary retention were seen in the study with no statistically significant difference in terms of complication rate between the two groups. No case of hypotension or bradycardia was seen. There was a significant difference between the two groups in terms of cardiovascular parameters (HR, SBP, DBP) after administration of drugs. CONCLUSIONS The addition of clonidine to ropivacaine for caudal blocks in children was associated with better quality of pain control and a longer duration of analgesia without any additional motor blockade. There was no significant difference seen in terms of complication. KEY WORDS Analgesia Duration, Caudal Analgesia, Clonidine, Pain Control, Ropivacaine.

Sedation and Delirium in the Intensive Care Unit—A Practice-Based Approach

Introduction: Critically ill patients often require sedation for comfort and to facilitate therapeutic interventions. Sedation practice guidelines provide an evidencebased framework with recommendations that can help improve key sedation-related outcomes. Materials and Methods: We conducted a narrative review of current guidelines and recent trials on sedation. Results: From a practice perspective, current guidelines share many limitations including lack of consensus on the definition of light sedation, optimal frequency of sedation assessment, optimal timing for light sedation and consideration of combinations of sedatives. We proposed several strategies to address these limitations and improve outcomes: 1) early light sedation within the first 48 hours with time-weighted monitoring (overall time spent in light sedation in the first 48 hours—sedation intensity—has a dose-dependent relationship with mortality risk, delirium and time to extubation); 2) provision of analgesia with minimal or no sedation where possible; 3) a goal-directed and balanced multimodal approach that combines the benefits of different agents and minimise their side effects; 4) use of dexmedetomidine and atypical antipsychotics as a sedative-sparing strategy to reduce weaning-related agitation, shorten ventilation time and accelerate physical and cognitive rehabilitation; and 5) a bundled approach to sedation that provides a framework to improve relevant clinical outcomes. Conclusion: More effort is required to develop a practical, time-weighted sedation scoring system. Emphasis on a balanced, multimodal appraoch that targets light sedation from the early phase of acute critical illness is important to achieve optimal sedation, lower mortality, shorten time on ventilator and reduce delirium. Ann Acad Med Singapore;49:215–25 Key words: Analgesia, Benzodiazepine, Critical Care, Dexmedetomidine, Propofol

Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain

Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient’s pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient’s pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioidinduced hyperalgesia in chronic neuropathic pain patients. Key words: Analgesia, hyperalgesia, carbamazepine, opioids, neuropathic pain, pharmacologic treatment

Different Analgesic Effects of Intrathecal Endomorphin-2 on Thermal Hyperalgesia and Evoked Inflammatory Pain in Ovariectomized Rats

Hormone replacement remains one of the common therapies for menopause-related pain but is associated with risk of orofacial or back pain. Spinal endomorphin-2 (EM-2) is involved in varied pain and its release is steroid-dependent, but whether increasing spinal EM-2 can inhibit thermal hyperalgesia and inflammatory pain in ovariectomized (OVX) female rats, an animal model mimicking menopause, is not clear, nor is the potential involvement of spinal mu-opioid receptor (MOR). In the current study, we revealed that the temporal decrease of spinal EM-2 is accompanied with OVX-induced thermal hyperalgesia that was dose-dependently attenuated by intrathecal (IT) delivery of EM2. The subcutaneous injection of formalin-induced inflammatory pain in OVX rats was exacerbated and IT delivery of EM-2 dose-dependently inhibited the inflammatory pain. However, the ED50 for IT delivery of EM-2 on thermal hyperalgesia is smaller than that on inflammatory pain in OVX rats, suggesting different contributions of the EM-2 system to these 2 pain modalities in OVX rats. IT pretreatment with MOR antagonist, betafunaltrexamine (β-FNA), attenuated IT EM-2 analgesia on both thermal hyperalgesia and inflammatory pain in OVX rats. Furthermore, IT delivery of EM-2 did not affect the animals’ locomotion or anxiety status. Our findings suggested that IT EM-2 might be a safer analgesia strategy than hormone replacement therapy in reducing risk of orofacial or back pain. However, a long-lasting form of EM-2 with less tolerance is needed to induce sustained analgesia. Key words: analgesia, intrathecal, endomorphin, ovariectomize, rat

Opioid Induced Hyperalgesia Altered with Propofol Infusion

Propofol is a common induction agent that is utilized worldwide in the field of anesthesiology. In recent years, its potential therapeutic role in a variety of patient states has been demonstrated. Controversy exists regarding Propofol mediated analgesic and antihyperalgesic properties. Recent studies have suggested a variety of different mechanisms of action, including modulation of N-Methyl-D- Aspartate receptors and the endocannabinoid system. The N-Methyl-D- Aspartate receptor is part of a larger family of glutamate receptors and is an important mediator of excitatory neurotransmission. In the case presented, the pain experienced by the patient was not well-controlled, in spite of increasing doses of opioids, potentially due to superimposed opioid induced hyperalgesia. In the present case, we demonstrate a cycle of opioid induced hyperalgesia which was successfully affected with a Propofol infusion. Controversial reports exist in animal studies on the analgesic properties of Propofol. Randomized controlled studies in animal models studying the effect of Propofol on pain sensation have shown that Propofol possesses an analgesic effect. This clinical case demonstrates that Propofol could possibly have antihyperalgesic effects on opioid induced hyperalgesia caused by high-doses of chronic opioids and worsened by fentanyl. We postulate that a probable mechanism of complete pain relief after the procedure could be the inhibition of activity of the N-Methyl-DAspartate receptor by Propofol because it was the only agent the patient received during the procedure, causing a break of the cycle of opioid induced hyperalgesia. Additional research is required to clarify Propofol mediated or modulated analgesic properties in humans. Key words: Analgesia, hyperalgesia, opioids, propofol, antihyperalgesia, anesthesia