To the Editor

An intriguing case occurred recently at our hospital. This case involves resistant hypotension refractory to treatment in a patient under general anesthesia with an implantable intrathecal device. This polypharmacy intrathecal pump was in place for pain control. The patient was scheduled for a revascularization of the lower extremities (aorto-bifemoral artery revascularization). The patient was an obese female with COPD, HTN, chronic pain, and peripheral vascular disease. The pain pump contained fentanyl, meperidine, bupivicaine and clonidine.

Intra-operatively, the patient appeared to have a high output, low SVR/PVR clinical state that was unresponsive to Neosynephrine, dopamine, epinephrine and norepinephrine. This patient reacted as if she was adrenergically nonresponsive or catecholamine depleted. Over the next sixteen days, the patient continued with this high cardiac output, low SVR/PVR state despite having a continual Levophed infusion. Ultimately the patient succumbed to multiorgan failure and respiratory complications. The differential diagnosis list was logically worked out with consults and labs. Briefly, cardiomyopathy and heart related problems ruled out, sepsis early on (she had catheter tip positive cultures 9 days post-op) ruled out, neuromuscular/spinal related catastrophes ruled out, endocrine problems ruled out, limb ischemia /lactic acidosis ruled out. Submucosal intestinal ischemia was never ruled out, but for it to have been a problem intra-operatively and continue for 3 weeks without becoming obvious on blood gases is unlikely.

This letter is to warn others of the potential problems with intrathecal pumps, specifically ones with alpha 2 agonist medication.

Studies have shown the hypotensive side effect of clonidine in whatever route given.^1-14 The clonidine dose used on this patient was on the low end, 55 micrograms a day. Some studies discuss high doses of 500 micrograms a day.¹⁵ No studies have investigated the neuromuscular, vascular or cardiovascular physiologic changes that can occur over long period of administration.

What’s the price of pain control? At what point do we say, turn it offÑbecause it’s all investigational. This mode of pain control is becoming more popular, and we all will encounter more such patients needing general and/or regional anesthesia. All I can say is it may be prudent to learn more about intrathecal drugs, their side effects, how to avoid side effects, how to turn the pumps off safely without withdrawal phenomenon and what the physiology behind long- and short-term effects of intrathecal clonidine.

Kyle Jones, MD
Gurley, AL

References

1. Chiari A,Christine L, Eisenach J., et al :Analgesic and Hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage labor. Anesthesiology. 1999;91:388-396.

2. Kock M, Gautier P, Pavlopoulou A, et al: Epidural Clonidine or Bupivicaine as the sole analgesic agent during and after abdominal surgery. Anesthesiology. 1999;90:1354-1362.

3. Eisenach JC, Lysak SZ, Viscomi CM: Epidural clonidine analgesia following surgery: phase 1 Anesthesiology. 1989 Nov;71(5):640-6.

4. Eisenach JC, Lavand’homme P, Tong C, Cieng JK et al: Antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist. Anesthesiology. 1999 Nov;91(5): 1425-36.

5. Dobrydnev IL, Tsygankova 01: Clinical experience in the use of clonidine in regional anesthesia and early postoperative period (1984-1989). Anesteziol Reanimatol. 1999 May-Jun;(3):4-12.

6. Ongioco R, Richardson CD, Rudner XL, Stafford-Smith M, Shcwinn DA. Alpha2 adrenergic receptors in human dorsal root ganglia: predominance of alpha 2b and alpha 2c subtype mRna. Anesthesiology. 2000 Apr; 92(4):968-76.

7. Khan ZP, Ferguson CN. Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999 Feb; 54(2):146-65.

8. Grubb MC, Stornetta RL, Pence R, et al: Antagonist precipitated clonidine withdrawal in rat: effects on locus coeruleus neurons, sympathetic nerves and cardiovascular parameters. J Anton Nerv Syst. 1998 Jul 15;71(2-3):85-95.

9. Del Carmen Garcia M, Enero MA, Celuch SM: Hypotensive and Hypertensive effects of catecholamines intrathecally injected in anesthetized rats. J Auton Nerv Syst. 1996 Jun 10;59(1-2):1726.

10. Gautier P, Kock M, Luc F, et al: Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology 1998;88:651-656.

11. Kimsha W, Chiari A, Krafft P, et al: Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks. Anesthesia & Analgesia. Vol 80:322-327.

12. Kital T, Kagawa K, Mammoto T et al: Supraspinal not spinal alpha 2 adrenoceptors are involved in the anesthetic sparing and hemodynamic stabilizing effects of systemic clonidine in rats. Anesthesia & Analgesia. 2000:90:722-726.

13. Benhamour D, Thorin D, Brichant IF et al: Intrathecal clonidine and fentanyl with hyperbaric bupivicaine improves analgesia during cesarean section. Anesthesia & Analgesia Vol 87:609-613.

14. Mercier F, Donnas M, Bouaziz H et al: The effect of adding a minidose of clonidine to intrathecal sufentanil for labor analgesia. Anesthesiology. 89:594-601, 1998.

15. Current Practices in intraspinal therapy, evidence based review of the literature on intrathecal delivery of pain medication, clinical guidelines for intraspinal infusion: report of an expert panel, future directions in the management of pain by intraspinal drug delivery: Special Section Polyanalgesic Consensus Conference 2000, Journal of Pain and Symptom Management 2000:20(2):sl-s50.