Drug Shortage Alert 8/1/2014

Transcription

1 Headquarters 500 Midway Drive Mount Prospect, Illinois USA Main Telephone Customer Service Facsimile Drug Shortage Alert 8/1/2014 Recommendations and information provided in Drug Shortage Alerts are compiled by experts in the field. Practitioners always are advised to consult with staff to ensure response to any drug shortage is in line with internal policies and procedures. Alternative Medications for Procedural Sedation (Adults >18 Years of Age) Introduction The Society of Critical Care Medicine s Drug Shortages Task Force has developed a guideline for procedural sedation that can be referred to for other options if a drug shortage arises with a particular class of medications. When utilizing less familiar medications for this indication, it is recommended to review basic principles of procedural sedation: Goals for sedation and analgesia: o Alteration of patient level of consciousness, mood and anxiety level o Amnesia of unpleasant sensation o Increase in pain threshold o Patient cooperation with appropriate response to tactile and verbal stimulation o Maintenance of intact airway o Maintenance of protective airway reflexes o Hemodynamic stability Procedural sedation is classified based on patient assessment into four categories: o Minimal sedation/analgesia: mild anxiolysis or pain control o Moderate sedation: purposeful response following voice or light touch o Deep sedation: purposeful response following painful stimuli o General anesthesia: no purposeful response to repeated painful stimuli Level of sedation can be an unpredictable, dynamic process based on pharmacokinetic and pharmacodynamic principles; therefore, it is recommended that providers utilizing unfamiliar medications be prepared to rescue patients from depth of sedation beyond the intended level based on institutional standards. o Use of anesthetic induction agents, including methohexital, propofol, and ketamine, should be consistent with institutional standards for deep sedation, regardless of route of administration and intended level of sedation. Characteristics of an ideal drug for procedural sedation and analgesia:

2 o Predictable pharmacokinetic profile Medications should be administered incrementally, allowing sufficient time between doses to assess effect o Rapid onset of action o Analgesic and anxiololytic effects Match medication duration of action with length of procedural stimulation o Short recovery time o Minimal associated risks Consider the patient s comorbidities when selecting drug, dose and administration interval, as patients with coexistent disease, extreme age, obesity, sleep apnea, and renal or hepatic insufficiency are more likely to develop complications associated with procedural sedation. o May be administered without the presence of an anesthesiologist Providers should make a distinction between analgesics that relieve pain (Table 1) and sedatives that decrease anxiety and promote somnolence (Tables 2 and 3). If both benzodiazepines and analgesics are used, consider: o Dose reduction of both agents o Giving an opioid first and titrating benzodiazepine to desired depth of sedation to minimize the risk of respiratory depression Reversal agents, including naloxone and flumazenil, should be available whenever opiates or benzodiazepines are administered. o Continued monitoring is recommended as the duration of action of the reversal agent(s) may be less than that of the agent it is intended to reverse. Table 1: Analgesia*

3 Drug Fentanyl Pharmacologic Class Opioid Approximate Parenteral Equianalgesic Dose 0.1 mg (100 mcg) Onset () 1-2 Duration min (duration prolonged with higher doses) Hydromorphone Opioid 1.5 mg hrs Morphine Opioid 10 mg hrs Intermittent mcg/kg mg mg/kg or 2-4 mg Remifentanil Opioid 0.1mg min Continuous Infusion Tier 1 # Tier 2 # Tier 3 # Loading dose: 0.5 mcg/kg Followed by mcg/kg/min continuous infusion Repeat Dosing/ Titration every (consider using lower ¼ to ½ of initial dose) every every (max 15 mg) Adjust by mcg/kg/min every 5 min (max of 0.2 mcg/kg/min) Side effects Reversal Safety Implications Special Comments Bradycardia, potentiated with propofol Nausea, vomiting, hypotension, bradycardia, pain at injection site, local tissue irritation bradycardia bronchospasm, pruritis, vomiting, chest wall rigidity Apnea, respiratory depression, chest wall rigidity, hypotension, bradycardia, post procedure nausea and vomiting. *Rapid titration of opiates may lead to hypotension and/or respiratory depression; #Tiers represent the order in which alternative agents should be considered. Naloxone Naloxone Naloxone Discontinue therapy Respiratory depression may last longer than analgesia Potential for potencyrelated dosing errors Side effects can be due to histamine release Risk of apnea and hypoventilation; only practitioners trained with airway management and anesthetic agents should administer Administer only as infusion Bolus dosing for general anesthesia only and not recommended due to risk of respiratory depression and muscle rigidity All lines should be flushed since small doses can cause significant adverse effects Less hypotension compared to morphine Accumulates with hepatic and renal impairment, which leads to an increased duration of effect Accumulates with hepatic and renal impairment, which leads to increased duration of effect Potency similar to fentanyl Ultra short acting Clearance unchanged with renal/hepatic insufficiency Not suitable as the sole agent for induction and should be used in conjunction with other agents In obese patients (>130% of IBW), use IBW for dosing 2

4 Table 2: Minimal to Moderate Sedation Drug Pharmacologic Class Onset Duration Midazolam () Benzodiazepine Lorazepam () Benzodiazepine Dexmedetomidine () Nitrous Oxide (Inhaled) α 2 -receptor agonist 15 (following start of infusion) Intermittent 0.02 mg/kg (2 mg increments) mg/kg or 1-2 mg (see safety implications) Continuous Infusion mcg/kg/hr Repeat Dosing/ Titration Tier 1* every 3-5 (max 0.2 mg/kg total) Tier 2* mg every (max 4 mg ) Adjust by mcg/kg/hr at least every 30 min (usual range mcg/kg/hr) Anesthetic Gas % *Tiers represent the order in which alternative agents should be considered; : not applicable Tier 3* Side effects Reversal Safety Implications Special Comments respiratory depression, paradoxical agitation respiratory depression, paradoxical agitation Bradycardia, hypotension Decreased myocardial contractility, worsening pulmonary hypertension, nausea, peripheral neuropathy, headache, CNS excitation, intracranial pressure Flumazenil Flumazenil Use with caution in patients who are obese or have acute kidney injury/chronic renal failure due to risk of accumulation of the active metabolite with repeated dosing; clearance is reduced when administered with medications that inhibit cytochrome P 450 enzyme systems. Reduce dose 25-50% if combined with opioids. Due to slower onset and longer duration of action, has limited utility in procedural sedation. Reduce dose by 25-50% if combined with opioids. Use with caution in patients with a history of heart block and those dependent on adrenergic tone to maintain blood pressure. Bolus dose increases risk of bradycardia, hypotension, and/or hypertension Requires a well-ventilated room and has potential for provider exposure or abuse; gas scavenging system minimizes provider exposure Can increase pressure in closed gas containing spaces pockets of air (e.g., pneumothorax, pneumoperitoneum / bowel obstruction, intraocular pressure, inner ear pressure, endotracheal tube cuff pressure) Consider patient-specific variables when determining dosage Consider patient-specific variables when determining dosage While dexmedetomidine provides mild analgesia, it will not blunt noxious stimuli and should not be used without adequate analgesia Can cause loss of oropharyngeal muscle tone; monitor for hypoxemia and hypoventilation (effects can be enhanced with concomitant benzodiazepine use) Administer with 30% oxygen to avoid diffusion hypoxia; oxygen should be continued after nitrous oxide discontinued. Typically used as adjunct to other sedatives. 3

5 Table 3: Moderate to Deep Sedation Drug Propofol Etomidate Ketamine Pharmacologic Class Sedative hypnotic Sedative hypnotic Dissociative anesthetic Onset () Duration Methohexital Barbiturate Intermittent mg/kg Continuous Infusion mg/kg mg/kg mg/kg *Tiers represent the order in which alternative agents should be considered. Repeat Dosing Side effects Reversal Safety Implications Special Comments mg/kg every 5 min Tier 1* Tier 2* 1-2 mg every 10 min mg/kg every 10 min 0.5 mg/kg every 2-5 min Tier 3* Pain at injection site, hypotension, myocardial depression, bradycardia, apnea, hypersensitivity reaction (allergy to eggs or soy), hypertriglyceridemia Emergence nausea/vomiting, adrenal suppression, myoclonous/seizure activity Emergence delirium, increased systemic and pulmonary pressures, intracranial and intraocular pressures, laryngospasm, hypersalivation, tachycardia myocardial depression, CNS and respiratory depression Small or large dose changes may result in an unpredictable general anesthetic state hypotension exaggerated when administered via central access Use caution in patients at risk for adrenal insufficiency Use caution in patients with significant coronary artery disease, increased intracranial/intraocular pressure and excessive respiratory secretions. Consider pretreatment with antisialogogue to minimize secretions. Hemodynamic stability maintained due to catecholamine release; use with caution in patients with poor reserve (e.g., elderly, trauma patients) and in patients with poor cardiac reserve due to direct myocardial depression. Unpredictable general anesthetic state may result, particularly with large doses Providers should be prepared to rescue patients from depth of sedation beyond the intended level Institutional procedures or state laws may preclude bolus administration by nurses Due to short duration of action, role in therapy may be for shorter procedures Consider pre-treatment with benzodiazepines to prevent associated emergence reactions Institutional procedures or state laws may preclude bolus administration by nurses Providers should be prepared to rescue patients from depth of sedation beyond the intended level 4

6 References: 1. ASHP Drug Shortage Resource Center. Accessed 3/17/ Baker SN, Weant KA. Procedural sedation and analgesia in the emergency department. J Pharm Pract. 2011;24: Bahn EL, Holt KR. Procedural Sedation and Analgesia: a Review and New Concepts. Emerg Med Clin N Am. 2005;23: Barr J, Zomorodi K, Bertaccini EJ, et al. A double-blind randomized comparison of lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model. Anesthesiology. 2001;95: Brown TB, Lovato LM, Parker D. Procedural sedation in the acute care setting. Am Fam Physician. 2005;71: Drug Information Handbook. 21 st Edition Lexicomp INC. 7. Gerlach AT, Murphy CV, Dasta JF. An updated focused review of dexmedetomidine in adults. Ann Pharmacother. 2009; 43: Gesin G, Barletta JF, Brown DR, Shander A. Recommendations for alternative analgesic and sedative agents in the setting of drug shortages. Critical Connections. 2012:11: Godwin SA, Caro DA, Wolf SJ, et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005;45: Gross JB, Bailey PL, Connis RT, et al. Practice guidelines for sedation and analgesia by non-anesthesiologists: an updated reported by the American society of anesthesiologists task force on sedation and analgesia by non-anesthesiologists. Anesthesiology. 96: Jones DR, Salga P, Meltzer J. Conscious sedation for minor procedures adults. N Engl J Med. 2011:364:e Keane MJ. Dexmedetomidine and procedural sedation. Anaesth Intensive Care. 2011;39: Meyers JL, Chadaudhuri S. Procedural sedation and analgesia: a practical review for non-anesthesiologist. J Surg Rad. 2011;2: Silverstein JH, Apfelbaum JL, Barlow JC, et al. Practice guidelines for postanesthetic care: a report by the American society of anesthesiologists task force on postanesthetic care. Anesthiology. 2002; 96(3): Weingart SD, Bhagwan SD. Current guidelines for procedural sedation in the emergency department. Anesthesiology. 2002;96: Balwinder Singh, Akhilesh Kumar Tiwari, Sanjay Kumar Verma, Pedro Whatts, Dipti Agarwal and Subhash Chandra (2012). Procedural Sedation and Analgesia in Emergency Department, Emergency Medicine An International Perspective, Dr. Michael Blaivas (Ed.), ISBN: , InTech, Available from: Contributed by: Katie Burenheide, MS, PharmD, BCPS, FCCM Mitchell J Daley, PharmD, BCPS Reviewed by: Scott Bolesta, PharmD, BCPS, FCCM Anthony T. Gerlach, PharmD, BCPS, FCCM Gail Gesin, PharmD Kevin W. Hatton, MD John J. Lewin III, PharmD, MBA, FCCM, FASHP Ravi S. Tripathi, MD 5