Ketamine in the Treatment of Acute Neuropathic Pain in the Treatment of Acute Neuropathic Pain!...
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Ketamine in the Treatment of Acute Neuropathic Pain Chris D Glover MD, Olga Pawelek MD, Hillary Cloyd RN. Department of Pediatrics and Anesthesiology. Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas. T-11 L-2 History A 120 kg male presents with a chief complaint of “shooting pains” in the right leg for over 1 month. His past medical history is significant for an extramedullary Intradural tumor, which had been partially resected at an outside facility. The patient reports a recent fall which has exacerbated his leg pain. He is scheduled today for laminectomy and tumor debulking with neurologic monitoring. Currently denies loss of bowel or bladder control. He denies motor weakness or loss in sensation. No other PMH noted. Intraoperative Course: •TIVA anesthetic •Fentanyl 400mcg •Sufentanil 118 mcg •Dexmedetomidine 45 mcg •Morphine 5 mg •Propofol infusion @100-150 mcg/kg/min through case. •Case stopped prematurely because of a diminution of the electrophysiologic monitoring on the left side with partial resection. •Extubation was uneventful and patient to PACU by 1200. PACU Course: •1225 - Pt reports “stomach pain” per RN nurse •1407 - Pain score of 10/10 after 150mcg of fentanyl and initiation of PCA pump (1.5mg basal / 2mg interval) •1445 - Pain persists with additional 100mcg fentanyl / Toradol 30mg given as bolus/ continued PCA use •1539 - Pain complaints persist after another 400mcg fentanyl / Morphine 9mg / Norco q4 •Tolerating PO at this point •Gabapentin 1100 mg given •1730 - Anxious and in pain with nursing notes indicating repeated PCA demands without relief. Ordered ketamine *1 – patient drifts to sleep •2200 - Abdominal pain with continuation of PCA and Norco Discussion (cont.): Neuropathic pain development can occur secondary to damage via central or peripheral means. At the peripheral level, hypersensitivity is thought secondary to the development of ongoing spontaneous activity, abnormal excitation, and increased sensitivity to stimuli by damaged axons post injury. Inflammation further results in the sensitization of nociceptors through alterations in the sodium channel. Ectopic activity of these nociceptors as well as increase in substance P lead to up- regulation of the sodium channels and alterations in calcium channels. At the central level, sensitization of dorsal horn neurons are amplified by peripheral nociceptors. Descending inhibitory pathways also lose some inhibition activity secondary to lower levels of inhibitory transmitters (GABA and glycine) in the spinal cord. N-methyl-D-aspartate (NMDA) receptor activation further lowers the nerve transduction threshold resulting in amplification of a stimulus to noxious levels. NMDA receptors are involved in sensory input at the level of the spinal cord, thalamus, limbic system, and cerebral cortex. The postulated mechanism of action of ketamine is that combination of nociceptive blockade with NMDA receptor antagonism is integral in reducing acute neuropathic pain. Low dose ketamine has been shown to attenuate of late cortical SSEP amplitude which correlates to changes in subjective pain perception. Conclusion: We present a case of acute neuropathic pain following intraspinal tumor debulking that was (not surprisingly) unresponsive to multimodal therapy consisting of opioids, ketorolac, acetaminophen, and neurontin who found sustained relief with subanesthetic bolus dosing of ketamine during acute flares of neuropathic pain. Use of ketamine in this patient report resulted in greater than 50% decrease in PCA use over the following 6 - 12 hours as indicated by our time/PCA use graph. The use of ketamine (bolus/infusion) has great utility in those who present with perioperative neuropathic pain. References: 1. Gray P. Acute Neuropathic Pain: Diagnosis and treatment. Current Opin Anesthesiol 21:590-595. 2008 2. Hayes C, Browne S, Lantry G, Burstal R. Neuropathic pain in the acute pain service: a prospective study. Acute Pain 2002; 4:45–48. 3. Hocking G, Cousins MJ. Ketamine in chronic pain management: An evidence-based review. Anesth Analg 2003;97:1730–40. 4. Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anaesthesiol 2007; 20:456–472 5. Schley M, Topfner S, Wiech K, et al. Continuous brachial plexus blockade in combination with theNMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain 2007; 11:299–308. 6. Eisenberg E, River Y, Shifrin A, Krivoy N. Antiepileptic drugs in the treatment of neuropathic pain. Drugs 2007; 67:1265–1289 Discussion : The definition of neuropathic pain as defined by the IASP is “pain caused by a lesion or disease of the somatosensory nervous system”. While neuropathic pain is commonly considered a chronic problem, it starts with an acute event and with time become chronic in nature. Acute neuropathic pain (ANP) presents a perplexing problem for clinicians especially in the perioperative arena. Conditions commonly associated with increasing the risk of acute neuropathic pain include trauma, HIV, herpes zoster, and transverse myelitis. Certain surgical procedures (amputation, thoracotomy, & mastectomy) also increase the likelihood of developing this condition. Diagnosis consists of a focused history and physical as well as implementation of a psychometric scale. Clinical features of potential ANP patients Pain resistant to opioids Allodynia on exam Numbness or pins and needles distribution Episodic sharp or burning pain Pain out of proportion to the injury Therapeutic options Tricyclic antidepressants (TCA’s) Selective serotonin reuptake inhibitors (SSRI’s) Anti-epileptics Tramadol NMDA receptor antagonists
Transcript of Ketamine in the Treatment of Acute Neuropathic Pain in the Treatment of Acute Neuropathic Pain!...
Ketamine in the Treatment of Acute Neuropathic Pain!Chris D Glover MD, Olga Pawelek MD, Hillary Cloyd RN.!
Department of Pediatrics and Anesthesiology. Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas.!
T-11!
L-2!
History!A 120 kg male presents with a chief complaint of “shooting pains” in the right leg for over 1 month. His past medical history is significant for an extramedullary Intradural tumor, which had been partially resected at an outside facility. The patient reports a recent fall which has exacerbated his leg pain. He is scheduled today for laminectomy and tumor debulking with neurologic monitoring. Currently denies loss of bowel or bladder control. He denies motor weakness or loss in sensation. No other PMH noted.!
Intraoperative Course:!• TIVA anesthetic!• Fentanyl 400mcg!• Sufentanil 118 mcg!• Dexmedetomidine 45 mcg!• Morphine 5 mg!• Propofol infusion @100-150 mcg/kg/min through case.!• Case stopped prematurely because of a diminution of the electrophysiologic monitoring on the left side with partial resection.!• Extubation was uneventful and patient to PACU by 1200.!
PACU Course:!• 1225 - Pt reports “stomach pain” per RN nurse!• 1407 - Pain score of 10/10 after 150mcg of fentanyl and initiation of PCA pump (1.5mg basal / 2mg interval)!• 1445 - Pain persists with additional 100mcg fentanyl / Toradol 30mg given as bolus/ continued PCA use!• 1539 - Pain complaints persist after another 400mcg fentanyl / Morphine 9mg / Norco q4!
• Tolerating PO at this point!• Gabapentin 1100 mg given!
• 1730 - Anxious and in pain with nursing notes indicating repeated PCA demands without relief. Ordered ketamine *1 – patient drifts to sleep!• 2200 - Abdominal pain with continuation of PCA and Norco!
Discussion (cont.): Neuropathic pain development can occur secondary to damage via central or peripheral means. At the peripheral level, hypersensitivity is thought secondary to the development of ongoing spontaneous activity, abnormal excitation, and increased sensitivity to stimuli by damaged axons post injury. Inflammation further results in the sensitization of nociceptors through alterations in the sodium channel. Ectopic activity of these nociceptors as well as increase in substance P lead to up-regulation of the sodium channels and alterations in calcium channels.!
At the central level, sensitization of dorsal horn neurons are amplified by peripheral nociceptors. Descending inhibitory pathways also lose some inhibition activity secondary to lower levels of inhibitory transmitters (GABA and glycine) in the spinal cord. N-methyl-D-aspartate (NMDA) receptor activation further lowers the nerve transduction threshold resulting in amplification of a stimulus to noxious levels. NMDA receptors are involved in sensory input at the level of the spinal cord, thalamus, limbic system, and cerebral cortex. !
The postulated mechanism of action of ketamine is that combination of nociceptive blockade with NMDA receptor antagonism is integral in reducing acute neuropathic pain. Low dose ketamine has been shown to attenuate of late cortical SSEP amplitude which correlates to changes in subjective pain perception.!
Conclusion:!We present a case of acute neuropathic pain following intraspinal tumor debulking that was (not surprisingly) unresponsive to multimodal therapy consisting of opioids, ketorolac, acetaminophen, and neurontin who found sustained relief with subanesthetic bolus dosing of ketamine during acute flares of neuropathic pain. Use of ketamine in this patient report resulted in greater than 50% decrease in PCA use over the following 6 - 12 hours as indicated by our time/PCA use graph. The use of ketamine (bolus/infusion) has great utility in those who present with perioperative neuropathic pain.!References:!1. Gray P. Acute Neuropathic Pain: Diagnosis and treatment. Current Opin Anesthesiol 21:590-595. 2008!2. Hayes C, Browne S, Lantry G, Burstal R. Neuropathic pain in the acute pain service: a prospective study. Acute Pain 2002; 4:45–48.!3. Hocking G, Cousins MJ. Ketamine in chronic pain management: An evidence-based review. Anesth Analg 2003;97:1730–40.!4. Gilron I. Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. Curr Opin Anaesthesiol 2007; 20:456–472!5. Schley M, Topfner S, Wiech K, et al. Continuous brachial plexus blockade in combination with theNMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees. Eur J Pain 2007; 11:299–308.!6. Eisenberg E, River Y, Shifrin A, Krivoy N. Antiepileptic drugs in the treatment of neuropathic pain. Drugs 2007; 67:1265–1289!
Discussion:!The definition of neuropathic pain as defined by the IASP is “pain caused by a lesion or disease of the somatosensory nervous system”. While neuropathic pain is commonly considered a chronic problem, it starts with an acute event and with time become chronic in nature. Acute neuropathic pain (ANP) presents a perplexing problem for clinicians especially in the perioperative arena. Conditions commonly associated with increasing the risk of acute neuropathic pain include trauma, HIV, herpes zoster, and transverse myelitis. Certain surgical procedures (amputation, thoracotomy, & mastectomy) also increase the likelihood of developing this condition. Diagnosis consists of a focused history and physical as well as implementation of a psychometric scale.!
Clinical features of potential ANP patients !
Pain resistant to opioids!
Allodynia on exam!
Numbness or pins and needles distribution!
Episodic sharp or burning pain!
Pain out of proportion to the injury!
Therapeutic options!
Tricyclic antidepressants (TCA’s)!
Selective serotonin reuptake inhibitors (SSRI’s)!
Anti-epileptics !
Tramadol!
NMDA receptor antagonists!
