Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Rinaldi F, de Denus S, Nguyen A, Nattel S, Bussieres JF. Drug shortages: patients and health care providers are all drawing the short straw. Can J Cardiol. 2017;33(2):283–6.
Fox ER, Sweet BV, Jensen V. Drug shortages: a complex health care crisis. Mayo Clin Proc. 2014;89(3):361–73.
Drug shortages roundtable. Minimizing the impact on patient care. Am J Health Syst Pharm. 2018;75(11):816–20.
Mazer-Amirshahi M, Fox ER, Zocchi MS, Pines JM, van den Anker JN. Longitudinal trends in U.S. shortages of sterile solutions, 2001–2017. Am J Health Syst Pharm. 2018;75(23):1903–8.
Roman A. The FDA and the pharmaceutical industry: is regulation contributing to drug shortage? Albany Law Rev. 2013;77(2):539–77.
Gupta DK, Huang SM. Drug shortages in the United States: a critical evaluation of root causes and the need for action. Clin Pharmacol Ther. 2013;93(2):133–5.
Fox ER, McLaughlin MM. ASHP guidelines on managing drug product shortages. Am J Health Syst Pharm. 2018;75(21):1742–50.
Statement from FDA Commissioner Scott Gottlieb, MD on the FDA’s work to mitigate shortages of intravenous drugs, shorten supply disruptions and better predict vulnerabilities.: U.S. Food & Drug Administration; 2018 [FDA Statement]. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm609453.htm. Accessed 5 Dec 2018.
Statement from FDA Commissioner Scott Gottlieb, M.D. on new steps to facilitate efficient generic drug review to enhance competition, promote access and lower drug prices [FDA Statement]. U.S. Food & Drug Administration; 2018. cited 2018. FDA Statement. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm591184.htm.
Fox ER, Tyler LS. Managing drug shortages: seven years’ experience at one health system. Am J Health Syst Pharm. 2003;60(3):245–53.
Bosma BE, van den Bemt P, Melief P, van Bommel J, Tan SS, Hunfeld NGM. Pharmacist interventions during patient rounds in two intensive care units: clinical and financial impact. Neth J Med. 2018;76(3):115–24.
McLaughlin M, Kotis D, Thomson K, Harrison M, Fennessy G, Postelnick M, et al. Effects on patient care caused by drug shortages: a survey. J Manag Care Pharm. 2013;19(9):783–8.
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23.
Tesoro EP, Brophy GM. Pharmacological management of seizures and status epilepticus in critically ill patients. J Pharm Pract. 2010;23(5):441–54.
Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61.
Current Issues: Drug Shortages: SCCM; 2018. http://www.sccm.org/Research/Current-Issues. Accessed 5 Dec 2018.
ASHP Drug Shortages List—Diazepam; 2018. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=330. Accessed 5 Dec 2018.
FDA Drug Shortages—Lorazepam: Food & Drug Administration; 2018 [FDA Drug Shortages]. https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=LorazepamInjection,USP&st=c&tab=tabs-1. Accessed 5 Dec 2018.
Burakgazi E, Bashir S, Doss V, Pellock J. The safety and tolerability of different intravenous administrations of levetiracetam, bolus versus infusion, in intensive care unit patients. Clin EEG Neurosci. 2014;45(2):89–91.
Cadena R, Shoykhet M, Ratcliff JJ. Emergency neurological life support: intracranial hypertension and herniation. Neurocrit Care. 2017;27(Suppl 1):82–8.
Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral oedema and intracranial hypertension. Crit Care Med. 2000;28(9):3301–13.
Bourdeaux CP, Brown JM. Randomized controlled trial comparing the effect of 8.4% sodium bicarbonate and 5% sodium chloride on raised intracranial pressure after traumatic brain injury. Neurocrit Care. 2011;15(1):42–5.
Corbett SM, Montoya ID, Moore FA. Propofol-related infusion syndrome in intensive care patients. Pharmacotherapy. 2008;28(2):250–8.
Mazer-Amirshahi M, Fox ER. Saline shortages—many causes, no simple solution. N Engl J Med. 2018;378(16):1472–4.
0.9% Sodium Chloride Large Volume Bags: American Society of Health-Systems Pharmacists; 2018. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=76. Accessed 6 Nov 2018.
Souba WWFM, Jurkovich GJ, Kaiser LR, Pearce WH, Pemberton JH, Soper NJ. Evolution of intraoperative fluid therapy for elective surgeries: historical and current fluid requirements. In: Ashley SW, editor. ACS surgery: principles and practice, 2 vol set. Toronto: Decker Intellectual Properties; 2014. p. 3216.
Dextrose Injection, USP [package insert]. Hospira, Lake Forest, IL; 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/016367s178lbl.pdf. Accessed 6 Nov 2018.
Peng ZY, Kellum JA. Perioperative fluids: a clear road ahead? Curr Opin Crit Care. 2013;19(4):353–8.
Raghunathan K, Shaw AD, Bagshaw SM. Fluids are drugs: type, dose and toxicity. Curr Opin Crit Care. 2013;19(4):290–8.
Patino AM, Marsh RH, Nilles EJ, Baugh CW, Rouhani SA, Kayden S. Facing the shortage of IV fluids—a hospital-based oral rehydration strategy. N Engl J Med. 2018;378(16):1475–7.
Urgent: Recall Notification Prothrombin Complex Concentrate (Human): US Food & Drug Administration; 2018. https://www.fda.gov/biologicsbloodvaccines/safetyavailability/recalls/ucm603830.htm. Accessed 9 Jan 2019.
Outbreak of Life-threatening Coagulopathy Associated with Synthetic Cannabinoids Use: Centers for Disease Control and Prevention; 2018. https://emergency.cdc.gov/han/han00410.asp. Accessed 9 Jan 2019.
Amerine LB, Chen SL, Daniels R, Key N, Eckel SF, Savage SW. Impact of an innovative blood factor stewardship program on drug expense and patient care. Am J Health Syst Pharm. 2015;72(18):1579–84.
Trueg AO, Lowe C, Kiel PJ. Clinical outcomes of a pharmacy-led blood factor stewardship program. Am J Ther. 2017;24(6):e643–7.
Frontera JA, Lewin JJ 3rd, Rabinstein AA, Aisiku IP, Alexandrov AW, Cook AM, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6–46.
Mohrien KM, Jones GM, Boucher AB, Elijovich L. Evaluation of a fixed, weight-based dose of 3-factor prothrombin complex concentrate without adjunctive plasma following warfarin-associated intracranial hemorrhage. Neurocrit Care. 2014;21(1):67–72.
Frontera JA, Gordon E, Zach V, Jovine M, Uchino K, Hussain MS, et al. Reversal of coagulopathy using prothrombin complex concentrates is associated with improved outcome compared to fresh frozen plasma in warfarin-associated intracranial hemorrhage. Neurocrit Care. 2014;21(3):397–406.
Edavettal M, Rogers A, Rogers F, Horst M, Leng W. Prothrombin complex concentrate accelerates international normalized ratio reversal and diminishes the extension of intracranial hemorrhage in geriatric trauma patients. Am Surg. 2014;80(4):372–6.
Cabral KP, Fraser GL, Duprey J, Gibbons BA, Hayes T, Florman JE, et al. Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding. Clin Neurol Neurosurg. 2013;115(6):770–4.
Switzer JA, Rocker J, Mohorn P, Waller JL, Hughes D, Bruno A, et al. Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage. Stroke. 2012;43(9):2500–2.
Voils SA, Baird B. Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter? Thromb Res. 2012;130(6):833–40.
Klein L, Peters J, Miner J, Gorlin J. Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal. Am J Emerg Med. 2015;33(9):1213–8.
Astrup G, Sarangarm P, Burnett A. Fixed dose 4-factor prothrombin complex concentrate for the emergent reversal of warfarin: a retrospective analysis. J Thromb Thrombolysis. 2018;45(2):300–5.
Abdoellakhan RA, Miah IP, Khorsand N, Meijer K, Jellema K. Fixed versus variable dosing of prothrombin complex concentrate in vitamin K antagonist-related intracranial hemorrhage: a retrospective analysis. Neurocrit Care. 2017;26(1):64–9.
Hall ST, Molina KC. Fixed-dose 4-factor prothrombin complex concentrate: we don’t know where we’re going if we don’t know how to get there. J Thromb Thrombolysis. 2018;46(1):50–7.
Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032–60.
Woo CH, Patel N, Conell C, Rao VA, Faigeles BS, Patel MC, et al. Rapid Warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate. World Neurosurg. 2014;81(1):110–5.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127–37.
Lexicomp Online, Lexi-Drugs Hudson, Ohio: Lexi-Comp, Inc.; 2018. https://online.lexi.com/lco/action/home. Accessed 15 Nov 2018.
FDA Drug Shortages—Aminocaproic acid: Food & Drug Administration; 2018. https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Aminocaproic%20Acid%20Injection,%20USP&st=r. Accessed 12 Nov 2018.
Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg. 2002;97(4):771–8.
FDA Drug Shortages—Abciximab (ReoPro) Injection: Food & Drug Administration; 2018. https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Abciximab+%28ReoPro%29+Injection&st=c&tab=tabs-1. Accessed 12 Nov 2018.
Wood S. Abciximab in ‘short supply’ worldwide TCTMD2018 [updated November 12, 2018; cited 2018 April 13, 2018]. https://www.tctmd.com/news/abciximab-short-supply-worldwide.
Kim S, Choi JH, Kang M, Cha JK, Huh JT. Safety and efficacy of intravenous tirofiban as antiplatelet premedication for stent-assisted coiling in acutely ruptured intracranial aneurysms. AJNR Am J Neuroradiol. 2016;37(3):508–14.
Jeong HW, Jin SC. Intra-arterial infusion of a glycoprotein IIb/IIIa antagonist for the treatment of thromboembolism during coil embolization of intracranial aneurysm: a comparison of abciximab and tirofiban. AJNR Am J Neuroradiol. 2013;34(8):1621–5.
Zhao W, Che R, Shang S, Wu C, Li C, Wu L, et al. Low-dose tirofiban improves functional outcome in acute ischaemic stroke patients treated with endovascular thrombectomy. Stroke. 2017;48(12):3289–94.
Memon MZ, Natarajan SK, Sharma J, Mathews MS, Snyder KV, Siddiqui AH, et al. Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischaemic stroke. J Neurosurg. 2011;114(4):1008–13.
Bartolone P. The other opioid crisis: hospital shortages lead to patient pain, medical errors. The Washington Post. 2018 December 9, 2018;Sect. Health & Science.
Injectable opioid shortages: suggestion for management and conservation: American Society of Health-System Pharmacists, Inc.; 2018. https://www.ashp.org/-/media/assets/drug-shortages/docs/drug-shortages-iv-opioids-faq-march2018.ashx. Accessed 9 Dec 2018.
Edillo PN. Drug shortages: a pharmacy informatics perspective 2009 [cited 2019 January 14, 2019]. https://www.pppmag.com/article_print.php?id=860.
Li J. Pharmacy OneSource Blog: balancing technology and teams to successfully navigate drug shortages and prevent patient harm: Wolters Kluwer; 2018. http://blog.pharmacyonesource.com/balancing-technology-and-teams-to-navigate-drug-shortages.
Gulbis BE, Ruiz MC, Denktas AE. The impact of drug shortages on the pharmacy, nursing, and medical staff’s ability to effectively care for critically ill patients. Crit Care Nurs Q. 2013;36(4):400–6.
Caulder CR, Mehta B, Bookstaver PB, Sims LD, Stevenson B. Impact of drug shortages on health system pharmacies in the southeastern United States. Hosp Pharm. 2015;50(4):279–86.
Niccolai C, Skledar S. Updating smart pump libraries during shortages. Pharm Purch Prod. 2012;9(4):8.
Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA. 2017;317(14):1433–42.
Klaus DA, de Bettignies AM, Seemann R, Krenn CG, Roth GA. Impact of a remifentanil supply shortage on mechanical ventilation in a tertiary care hospital: a retrospective comparison. Crit Care. 2018;22(1):267.
Mazer-Amirshahi M, Goyal M, Umar SA, Fox ER, Zocchi M, Hawley KL, et al. U.S. drug shortages for medications used in adult critical care (2001–2016). J Crit Care. 2017;41:283–8.
Source of support
There was no funding granted/needed for this manuscript by or from any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval/informed consent
This article does not contain any studies with human participants or animals performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Clark, S.L., Levasseur-Franklin, K., Pajoumand, M. et al. Collaborative Management Strategies for Drug Shortages in Neurocritical Care. Neurocrit Care 32, 226–237 (2020). https://doi.org/10.1007/s12028-019-00730-7
- Drug shortages
- Natural disasters
- Medication errors
- Patient care
- Neurocritical care