Dexmedetomidine for acute clonidine withdrawal following intrathecal pump removal: A drug beginning to find its expanding niche

Management of chronic non-cancer pain by intrathecal delivery is gaining increasing use despite lack of evidence of efficacy and long-term safety. ¹ The development of drug tolerance due to these devices can precipitate life-threatening withdrawal syndromes if drug delivery is ceased. Clonidine is a centrally acting α2 agonist and has level II evidence for intrathecal use, either as a single or combined agent in the management of chronic neuropathic pain. ² Serious complications from acute clonidine withdrawal due to intrathecal pump malfunction have been reported, such as the development of stress-induced cardiomyopathy. Previous case reports have described the use of intravenous clonidine and benzodiazepines to manage the acute withdrawal syndrome. ³

We admitted a patient to the intensive care unit (ICU) due to life-threatening sequelae of acute clonidine and opioid withdrawal following the removal of an infected intrathecal pump 48 h prior. The withdrawal was characterised by hyperactive delirium; blood pressure 280/190 mmHg: sinus tachycardia 165 beats/min. The patient had been previously receiving; intravenous morphine infusion; twice daily oral dosing of clonidine; additional intravenous clonidine. She required intubation and ventilation to control her physiological derangement and delirium. The initial use of opioids, benzodiazepines and propofol did not result in a resolution of her severe tachycardia, and unfortunately led to hypotension requiring numerous aliquots of vasopressor medication. Dexmedetomidine was commenced at a dose of 1 µg/kg/h with no initial bolus, enabling a cessation of the midazolam, and significant weaning of the propofol. After 60 min, there was a sustained episode of hypotension leading to a reduction in the Dexmedatomidine dose to 0.4 µg/kg/h, which achieved cardiovascular stability with a blood pressure of 150/90 mmHg and a heart-rate of 64 beats/min. The patient was extubated 48 h after intubation on 0.4 mcg/kg/h dexmedetomidine and morphine 2 mg/h. She discharged from ICU on day 3 pain-free, having being re-started on oral clonidine, and continued on intravenous opioids.

The pharmacological profile of dexmedetomidine when compared to clonidine may confer possible benefits in this particular population due to an eight-fold greater selectivity and specificity for α₂ versus α₁ adrenoceptors, along with known nociceptive effects leading to a subsequent reduction in opioid requirements. ⁴ The ability to titrate a continuous infusion rather than administer boluses of clonidine also offered greater cardiovascular stability.

The use of dexmedetomidine for sedation in ventilated patients in ICU is approved by the food and drug administration (FDA), and the ongoing SPICE III study may further establish its role in sedation and prevention of delirium in ICU patients. Its use beyond this setting is also gaining interest with case series evaluating its role in acute alcohol withdrawal, ⁵ and in procedural sedation to provide effective sedation and analgesia without causing significant respiratory depression and blunting of airway reflexes. ⁶ While we are not claiming that dexmedetomidine is a ‘magic bullet’, however, it makes sense that with the changing ICU patient demographic, especially patients with a significant history of alcohol and substance abuse, we may need to tailor our traditional sedation regimens to optimise patient outcomes.