Challenges in Managing a Patient with Refractory Shock due to Telmisartan Overdose
Corresponding Author: Pooja R Murthy, Department of Critical Care Medicine, Manipal Hospital, Bengaluru, Karnataka, India, Phone: +91 809769070976, e-mail: firstname.lastname@example.org
Angiotensin receptor blockers are commonly used to treat hypertension. However, the toxicity of this medication can be life-threatening and can cause severe hypotension and refractory shock. There are no case reports or published guidelines for its management. We hereby present a case of a young female with telmisartan overdose who was managed with multiple vasopressors and rescue therapies like methylene blue, high-dose glucose-insulin infusion, ascorbic acid, thiamine, steroids, and other agents. Early detection and intensive management of refractory shock are necessary to prevent mortality.
How to cite this article: Murthy PR, Ravi GK, Gupta KVV, et al. Challenges in Managing a Patient with Refractory Shock due to Telmisartan Overdose. J Acute Care 2022;1(1):26-28.
Source of support: Nil
Conflict of interest: None
Keywords: High-dose insulin—dextrose, Methylene blue, Refractory shock, Telmisartan
Cardiovascular drug overdose is rare, accounting for only 1% of all overdose presentations. These drugs have serious adverse effects and may lead to high morbidity and mortality.1 In-hospital mortality of circulatory shock requiring vasopressors exceeds 50% and nearly 40% of these deaths are caused by progressive hypotension despite chemical and mechanical support.2 Telmisartan is an angiotensin receptor blocker (ARBs). ARBs toxicity is rarely reported in the literature. Here we present a case of refractory shock following telmisartan overdose in a young woman and the challenges faced in the evaluation and maintaining hemodynamic stability prior to successful discharge to home.
A 31-year-old woman, with no prior illnesses, was assessed in the emergency room (ER) following revelation to her partner about a total oral consumption quantity of telmisartan 400 mg and paracetamol 5 gm about 10 hours prior to her presentation. An hour prior to her ER presentation, a primary care physician undertook a gastric lavage and rushed her to our tertiary care center.
She was lethargic but conscious and coherent during the initial examination. She confirmed the dosages of medications consumed as well. The cardiovascular examination noted warm peripheries and a heart rate of 82/minute but with a blood pressure (BP) of 60/30 prompting emergent fluid resuscitation. Following 1500 mL of crystalloid fluid resuscitation during the initial hour, she remained hypotensive necessitating initiation of noradrenaline of 0.1 mcg/kg/minute. Due to significant hemodynamic instability, she was initiated on supplemental oxygen despite her room air SpO2 is 95%. Blood gas analysis at admission to ER showed significantly raised lactate with moderate to severe metabolic acidosis (BE: -15.3).
She was transferred to the intensive care unit (ICU) as she required continuous infusion of vasoactive medication to improve perfusion pressure. She required a noradrenaline dose of 0.5 mcg/kg/min to maintain a BP of 70/40 mm of Hg (heart rate of 120 per minute) at the initial assessment in ICU. During the hour elapsed from the time of arrival to ER and admission to ICU, she started to become restless with continued worsening in the hemodynamic state.
She underwent a point of care ultrasound to assess the shock state and it noted a hyperdynamic left ventricular ejection fraction (LVEF). Preload assessment noted an IVC collapsibility index of 60%. Noting the above she received further crystalloid fluid bolus along with escalating doses of noradrenaline. Over the next 2 hours, despite the fluid resuscitation, she required initiation of adjunct vasopressin infusion of 0.04 units/min and adrenaline infusion of 0.1 mcg/kg/min for refractory hypotension (Fig. 1).
Due to progressively worsening circulatory collapse and increasing restlessness, she required immediate initiation of mandatory mode mechanical ventilation along with deep sedation. Monitoring of acid-base state noted a worsening metabolic acidosis in conjunction with serum lactate levels making a decision to start continuous renal replacement therapy imminent (Fig. 2).
Despite the multiorgan support, she continued to have poor perfusion pressure during the initial 4 hours of ICU stay requiring the addition of not so commonly used phenylephrine infusion as a fourth vasoactive medication.
Though the assessment noted a vasoplegic state, as the circulatory collapse was secondary to anti-hypertensive agents, other rescue therapies were initiated following the risk-benefit assessment. She received a high dose insulin-dextrose infusion (insulin of 0.5U/kg/hr. and 50% dextrose at 50 mL/hr.) Insulin-dextrose infusion was titrated to a goal of >70 mm Hg. She also received intravenous formulations of ascorbic acid 1.5 gm every 6 hours and thiamine 200 mg every 12 hours as part of rescue therapies. N-acetyl cysteine (as per Prescott regimen) was added to other therapies for intake of subtoxic dose paracetamol. Her liver function test and coagulation profile pattern showed only minor changes consistent with circulatory shock.
As circulatory collapse was imminent a referral to the cardiac team for mechanical circulatory support was made and a decision against the use of an extracorporeal membrane oxygenator was made due to the severe vasodilatory nature of the shock. At this juncture, a decision to use methylene blue at a dose of 2 mg/kg given over 1 hour was made in desperation.
Following the above interventions within the first 12 hours of her ICU stay, she managed to maintain a mean arterial pressure of 55–60 mm Hg initially and consistently above 65 mm Hg over the next 48–72 hours. On day 3 of the ICU stay, she was off vasopressor support and was able to tolerate spontaneous breathing trials (SBT). She was also noted to start making urine (1 mL/kg/hr). Noting above and on passing SBT, she was liberated from mechanical ventilation and on day 5 transitioned to ward level care. Following physical and psychological evaluation, she was discharged home 7 days following her index admission with no residual organ dysfunction.
Telmisartan acts on AT1 receptors and causes profound vasodilation. It is one of the rare causes of vasoplegic shock from a drug overdose. Search for “Telmisartan overdose” in various search engines resulted in finding a few case reports and series along with opinion or review articles.
Telmisartan overdose is rare and its presentation as a circulatory collapse is even rarer. In a review of poison center referrals for cardiovascular drug overdose in Europe by Dagmar et al, it is noted only 8% of cases are due to Telmisartan.3 Less than 10% of these developed moderate symptoms and required hospitalization. Based on symptoms and dosage of drug consumption, a maximum daily dose for adults adjusted to body weight (MDDw) was derived. Our patient had MDDw of 5-fold and consistent with the above study, she developed symptoms requiring hospitalization.
Mathias et al. reported the patients with valsartan overdose to a poison control center in Texas.4 Out of 185 exposures, 7% (13 patients) had serious outcomes. The severity depended on the dose and circumstances of exposure to the drug.
Telmisartan causes refractory vasodilatory shock. Various rescue therapies have been described for hemodynamic management of refractory shock. This includes high-dose insulin-dextrose infusion, methylene blue, a combination of vitamin C, thiamine, and hydrocortisone and angiotensin II (ATII)5.
High-dose insulin-dextrose infusion may be beneficial in ARBs toxicity as they act by G-protein-coupled receptors similar to beta-blockers and calcium channel blockers,6 but their efficacy is yet to be proven.
Methylene blue has growing evidence of its use as adjunctive therapy in refractory vasoplegic shock caused after cardiac bypass or by sepsis or anaphylactic shock. Manji et al.6 have used it in undifferentiated vasoplegic shock and found it to be beneficial. Kalkan et al reported that in patients with severe undifferentiated vasoplegic shock that is unresponsive to vasoactive agents, there is potentially a role for use of a single dose of methylene blue as rescue therapy.7,8
Vitamin C, thiamine, and hydrocortisone have been used as a combination therapy and have shown to be of benefit in some studies. A recent study published in January 2020 did not show any rapid resolution of septic shock when used in combination compared to hydrocortisone alone.9 In our patient, we used the above rescue therapies for refractory vasodilatory shock.
Few other therapies noted are intralipid and VA ECMO. Sundar et al. case report using VA ECMO in a patient with combined amlodipine and telmisartan overdose. Our patient developed vasodilatory shock with a high normal ejection fraction; hence a peripheral VA ECMO as a rescue measure may have been a choice to reduce the vasoactive medication dosages.
The role of angiotensin II has been demonstrated in patients with distributive, cardiogenic, and other forms of shock, including hypotension associated with, angiotensin-converting enzyme (ACE) inhibitor overdose, dialysis, and perioperative hypotension.10 This drug couldn’t be used due to nonavailability.
Telmisartan and other ARBs can lead to refractory vasoplegic shock and in turn multi-organ dysfunction syndrome. Due to the lack of high-quality literature and a clear guideline, an approach that involved aggressive crystalloid resuscitation, the standard protocol of escalating vasoactive medication use, and various rescue and experimental therapies following risk-benefit evaluation are likely to help improve morbidity and mortality in such life-threatening situations. Use of intralipid, angiotensin II and VA ECMO are other options that can be tried.
Pooja R Murthy https://orcid.org/0000-0001-5870-1078
Gopala K Ravi https://orcid.org/0000-0001-7343-0624
Venkatesha Gupta KV https://orcid.org/0000-0003-4344-3840
Justin A Gopaldas https://orcid.org/0000-0002-0420-6925
Poonam P Rai https://orcid.org/0000-0003-2279-4967
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6. Manji F, Wierstra B, Posadas J. Severe undifferentiated vasoplegic shock refractory to vasoactive agents treated with methylene blue. Case Rep Crit Care 2017;2017:8747326. DOI: 10.1155/2017/8747326
8. Moskowitz A, Andersen LW, Huang DT, et al. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care 2018;22(1):283. DOI: 10.1186/s13054-018-2217-4
10. Sundar SS, Madhusoodhanan NN, Siroraj AP, et al. Extracorporeal membrane oxygenation for cardiotoxic drug overdose- a lifesaving intervention. J cardiac crit care TSS 2017;1(2):105–107. DOI: 10.1055/s-0038-1626678
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