ALTERNATIVAS A LA ADMINISTRACION: OPIOIDES IT

Transcription

1 ALTERNATIVAS A LA ADMINISTRACION: OPIOIDES IT Oscar A. de Leon-Casasola, MD Professor of Anesthesiology and Medicine Senior Vice-Chair Dept. of Anesthesiology, The Jacobs School of Medicine Chief, Pain Medicine and Professor of Oncology Roswell Park Cancer Institute Buffalo, NY

2 Conflictos de Interes Ninguno que reportar

3 Potential Indications for IT Rx Pain in cancer patients not responding to multimodal pharmacological therapy, including: Upper abdominal neoplasms with metastasis outside of the visceral capsule Paravertebral metastatic masses with foraminal involvement Post-herpetic neuralgia Chemotherapy induced peripheral neuropathy Compression fractures with severe foraminal stenosis with both somatic and neuropathic components Small fiber neuropathy associated to paraneoplastic syndromes Post-surgical pain syndromes in whom PNS is not a choice

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5 What do these conditions have in common? The high likelihood of a neuropathic pain component Consequently, the use of opioid alone, will not result in adequate pain control Thus, at this point compounding is necessary

6 Is there evidence on this regard?

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8 Results at 1 Month Pain reduction (VAS) 39.1% for CMM, 51.5% for IDDS Composite toxicity (CTC) 17.1% for CMM, 50.3% for IDDS (P=0.004) Side effects (CTC) Fatigue and depressed level of consciousness significantly less with IDDS than CMM (P<0.05) Impotence and pruritis worsened with CMM Smith T. et al. J Clin Oncol 2002;20:4040

9 CMM vs IDDS High prevalence of NeuP/Mixed Pain (75%) Limited IT use of bupivacaine/clonidine Smith TJ, et al. J Clin Oncol, 20(19):4040, 2002

10 However, if an opioid is to be used alone, which one should I use?

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25 Starting Therapy Titration to achieve adequate pain control is performed every 5-7 days: Increase the opioid concentration by 25% if somatic pain Increase the bupivacaine until a dose of 20 mg/day is achieved if the tip of the catheter is above T12 or 10 mg /day if below L1 Increase clonidine up to 1.5 mg/day

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29 IS INTRATHECAL HYDROMORPHONE AT DOSES GREATER THAN 10 MG PER DAY SAFE? Cohen IW 1,2,3, Tokorcheck J 1,2,3, Matson B 1,3, Renner RR 1, Grimmer JE 1, Bentley-McLachlan MJ 1, de Leon-Casasola O 1,2 Introduction The 2017 Polyanalgesic Consensus Conference (PACC) recommendations on intrathecal (IT) therapy suggests a maximum hydromorphone (H) concentration of 15 mg/ml and a maximum dose of 10 mg/day. 1 However, we could not find in the manuscript any evidence to support those recommendations. Moreover, they stated that no new studies investigating the efficacy of IT H in the treatment of chronic pain. Thus, we retrospectively review our IT therapy database to determine both the efficacy and safety of high doses of IT H. Materials & Methods IRB approval for retrospective chart review was obtained, need for patient consent was waived. Data reviewed from 33 patients with intrathecal pumps between 1/1/2001 to 8/1/2017. Seven patients with IT H doses greater than the PACC recommendations were found. All patients received a dose of 0.5 ml/day and the medication was compounded by one single pharmacy. H was always compounded with bupivacaine (B), clonidine (C), or both. The entire duration of the IT H was identified and any side effects or changes in therapy were noted. The number of days of therapy (DOT) was calculated on a per-patient basis. Maximum possible risk (MPR) was calculated using the inferential rule of three based on zero toxic events and total DOT at a 95% confidence interval. 2 1 Roswell Park Cancer Institute; 2 University at Buffalo; 3 Buffalo Veteran Affairs Medical Center Maximum Possible Risk Results Six patients received therapy with H+B+C, one patient with H+C. Patients received a mean of days of therapy with a range of 124 to 5125 days above the PACC recommendations without H related neurotoxicity, total DOT MPR based on DOT was calculated to be %. None of the patients required reduction in IT H dose secondary to side effect. There was not a single instance of catheter tip granuloma. One patient had a dose reduction unrelated to toxicity from 20mg/ ml to 14mg/mL. This was increased to 18mg/mL four months later due to progression of disease. Another patient transferred care to our clinic 8 years after pump placement which was subsequently removed 5 years later due to an infection. We only report data available during the time under our care. Discussion Patients in this report received a mean of 90 months (4.13 to months range) of IT H therapy with concentrations greater than 15mg/mL and/or doses greater than 10 mg/day without evidence of neurotoxicity or catheter tip granuloma. Accounting for length of therapy and with zero incidences of toxicity, the maximum possible risk is only % at a 95% confidence interval. 2 We are not aware of any study documenting evidence of neurotoxicity after IT H administration and this analysis further supports this notion. Moreover, we believe that patients did not experience catheter tip granulomas, despite the high concentrations and daily doses because of the infusion rate used in every single patient. Table Patient data set including diagnoses, IT agents, and total DOT References 1. Deer TR, et al. Neuromodulation 2017;20:96 2. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983; 1;249(13):1743-5

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33 IT Lipidsoluble Opioids IV versus IT potency after a single shot administration: When administered IV, sufentanil is X more potent than morphine (weight:weight) in terms of analgesic efficacy When administered IT, sufentanil is only 10X more potent than morphine This is also explained by terms of spinal cord exposure Lu JK, et al. Anesth Analg. 1997;85:372.

34 IT Lipidsoluble Opioids Similarly, fentanyl is 100X more potent than morphine when administered IV However, it is only 4X more potent when given IT Willens JS, et al. Heart Lung. 1993;22:239. Palmer CM, et al. Anesthesiology. 1998;88:355.

35 Why does that occur after a single shot administration?

36 Spinal Cord Volume of Distribution The drug s cord volume of distribution is important in this regard: Morphine s Vcord value: 7.9 ml Sufentanil s Vcord value: 101 ml It appears that the larger the Vcord value, the greater the distribution in the white matter and myelin of the spinal cord, limiting distribution in the gray matter Ummenhofer WC, et al. Anesthesiology. 2000;92:739.

37 The Concept of Intrinsic Efficacy

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39 The Concept of Intrinsic Efficacy Opioid agonists (morphine, fentanyl, sufentanil, etc.) were believed to have equal maximum analgesic efficacy when equivalent doses were used. However, it has been suggested that maximum analgesic effect may be achieved while they occupy different proportions of the available receptors subtypes. Agents that require low receptor occupancy while exerting a maximum analgesic effect (sufentanil) are defined as having a higher intrinsic efficacy

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44 Prospective study of 3 year follow up of low dose intrathecal opioids in the management of chronic nonmalignant pain n=61 patients; 6.2 year duration of pain Worst and average VAS: 8.9 and 7.5 decreased to 4.0 and 3.4 at 36 months (p=0.012 and p<0.001) Reduction in oral opioid consumption meq MSO4/day to 3.8 meq/day at 3 months IT dose remained low: 1.4 mg/day at 6 months and 1.48 mg/day at 36 months Improvement in physical and behavioral function Hamza, et al. Pain Med 2012; 13:

45 Failure to Achieve Pain Control Pump failure: Computer-program analysis for volume and the volume present within the pump needs to be within 10% of each other, otherwise pump failure is suspected.

46 Failure to Achieve Pain Control Is there a neuropathic pain component and the patient is only receiving IT opioids?

47 Failure to Achieve Pain Control Has the tip of the catheter migrated?

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49 Failure to Achieve Pain Control If none of these aforementioned alternatives are not an issue, then one must rule out catheter disconnection

50 Failure to Achieve Pain Control Catheter: A myelogram performed through the diagnostic port of the pump will be necessary to determine if the device is obstructed, disconnected, or the tip of the catheter is in the correct position. The diagnostic port of the pump can accommodate only a 25-gauge Huber needle. It is important to consider the dead space of the catheter when injecting the contrast medium, particularly if a high concentration of medications is being used

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55 Intrathecal Therapy in Cancer If mechanical problems are not present then consider recurrence of disease or tumor progression Intrathecal infusions at a rate of 0.5 ml/day produce segmental analgesia Bupivacaine has a limited spread when administered at that rate Kotob F, et al. ASA Abstract A347, 2006 Bernards CM. Anesthesiology 2006; 105:169 78

56 Intrathecal catheter T-8 Mesothelioma

57 Bernards CM. Anesthesiology 2006; 105: After 8 h infusion at 20 mcl/h Posterior SC Later SC Anterior SC

58 Conclusions IT therapy with opioids alone is NOT an appropriate option for patients who do not respond to oral pharmacological therapy IT bupivacaine and clonidine are appropriate adjuvants to improve the success rate of this therapeutic alternative However, appropriate IT adjuvant titration based on a pathophysiologic analysis is necessary to obtain appropriate results