Article Text
Abstract
Case presentation A woman in her 70s was found unresponsive and brought to our hospital with respiratory distress, cardiomyopathy and volatile alternation between hypotension and hypertension. She was intubated and admitted to intensive care for supportive treatment of suspected baclofen overdose. She gradually recovered and was discharged 10 days after presentation. Laboratory testing confirmed baclofen overdose.
Conclusion This case illustrates the classic features of baclofen toxicity but also includes unusual features including ST elevations on ECG and apical ballooning on echocardiogram. Lack of immediate laboratory testing can be a significant diagnostic challenge, so a high index of suspicion is needed to definitively diagnose baclofen overdose. Furthermore, haemodynamic volatility requires careful and frequent re-evaluation of treatment, so early recognition and anticipation of complications are essential for effective management of this life-threatening condition.
- Cardiovascular system
- Poisoning
- Adult intensive care
- Toxicology
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Background
Baclofen overdose by ingestion is relatively uncommon, and measurement of serum baclofen levels may take days to weeks. Thus, oral baclofen overdose is often diagnosed clinically rather than objectively.
Case presentation
A woman in her 70s with a relevant medical history of anxiety, post-traumatic stress disorder, hypertension and hypothyroidism was found by a family member to be unresponsive and in respiratory distress in bed at home. An empty bottle of baclofen was found nearby, and downtime was unknown.
Emergency medical services (EMS) were called. The patient was intubated at the scene; no medications were necessary for intubation. On the way to the emergency department (ED), she was agitated and uncomfortable with ventilation and was given a total of 12 mg midazolam and 150 mcg fentanyl intravenously for sedation. She also received a bolus of intravenous crystalloid fluid. A 12-lead ECG obtained during transport revealed ST elevations in anterior leads with reciprocal depressions in leads V1 and V2. The first ECG performed in the ED (figure 1) demonstrated sinus bradycardia with a rate of 58 beats per minute with left axis deviation of −72°, a right bundle branch block (RBBB) with a QRS of 130 ms and a QTc of 479 ms. A repeat ECG performed 1 hour later (figure 2) revealed persistent bradycardia at 48 beats per minute. The RBBB on the initial ECG was replaced by a non-specific conduction block.
Vital signs were initially notable for hypertension; blood pressure during EMS transport was 244/142, and initial pressure in the ED was 156/102. She had intermittent episodes of hypotension in the ED with blood pressures as low as 34/20 and received an additional 2 litres of intravenous normal saline. These blood pressure readings were recorded with an automated cuff with several repeated readings reflecting severe hypotension. The blood pressure began to rise, while the patient remained bradycardic, so it is unlikely that the hypotension was reflective of heart rate variability. She required a norepinephrine drip titrated from 0.02 to 0.08 mcg/kg/min for 2 hours. This was transitioned to phenylephrine for an additional 6.5 hours with dose ranges from 0 to 75 mcg/min. Activated charcoal was not administered because the patient likely ingested baclofen more than 1 hour prior to arriving in the ED. Multidose-activated charcoal was not administered because the drug is predominately cleared renally, and baclofen is not one of the drugs where multidose-activated charcoal is recommended. CT in the ED showed no significant radiographic abnormalities of her head, neck, chest or abdomen. Initial laboratory studies revealed several metabolic abnormalities, including respiratory acidosis (pH 7.22, pCO2 60.0, pO2 34, HCO3 24.5, base deficit 4 via arterial blood gas), hypokalemia (3.1 mmol/L) and elevated troponin (0.175 ng/mL). There was no evidence of acute or chronic renal failure as evidenced by normal creatinine and blood urea nitrogen throughout hospitalisation. Because baclofen is cleared renally and the creatinine clearance remained adequate the entire time, enhanced elimination using dialysis was not considered. A urine drug screen was ordered, but there was insufficient sample for results. Baclofen level was drawn on presentation, but the elevated result via liquid chromatography/tandem mass spectrometry (4.4 mcg/mL, therapeutic range 0.08–0.40 mcg/mL per the specific laboratory test) was not known until 2 weeks later. Poison control was contacted regarding treatment options. Their recommendations included symptomatic treatment of hypotension with intravenous fluids and vasopressors as needed to maintain a mean arterial pressure of 65 mm Hg. There was a discussion that severe hypertension may develop, and it should be treated as a hypertensive urgency/emergency with vasodilators such as nicardipine.
Considering the abnormal ECG and elevated troponin, an echocardiogram was obtained after admission and showed ballooning and akinesis of the apex concerning for takotsubo cardiomyopathy (figure 3). Takotsubo cardiomyopathy is not typical of baclofen toxicity, and this pathology likely resulted from her family situation combined with severely elevated blood pressure causing immense cardiac stress. This extremely stressed state mixed with periods of hypotension likely caused the elevated troponin. Cardiac catheterisation performed about 12 hours after hospital presentation showed no evidence of coronary artery disease.
The patient remained intubated in the medical intensive care unit (MICU) for supportive management and observation for over 24 hours. Supportive measures included mechanical ventilation, electrolyte repletion, intravenous hydration with lactated Ringer’s and pharmacologic management of hypo- and hypertension. During that time, continuous electroencephalography (EEG) showed no electrographic seizures. Her systolic blood pressure on the second day of admission ranged between 150 and 230 mm Hg with diastolic blood pressures between 80 and 140 mm Hg, so a nicardipine drip was started. This hypertension alternated with hypotension requiring alternation between nicardipine and norepinephrine infusions.
Approximately 36 hours after presentation to the hospital the patient’s neurological and respiratory function improved, she exhibited strong cough and gag reflexes and required minimal ventilatory support. She was therefore extubated. Her mentation and haemodynamics gradually improved, and by the fourth day of her hospital stay, intravenous medications to address her blood pressure were discontinued. She was deemed medically stable for transfer out of the MICU.
At the time of downgrade from the MICU, a psychiatric consultation was requested. The patient confirmed that she indeed intentionally ingested an excess of baclofen; she reported severe distress related to frustration from extreme tensions with her child which she felt were not adequately addressed by agencies who had investigated the patient’s allegations of abusive behaviour. Inpatient psychiatric admission was recommended, and the patient agreed to this. She remained medically stable and was discharged approximately 10 days after hospital presentation.
Outcome and follow-up
The patient was discharged to a psychiatric facility, treated and eventually discharged home where she remains.
Discussion
A literature review was conducted using the PubMed database by searching for ‘baclofen overdose’. The 187 returned results were narrowed down to journals with reports published between 1980 and 2022 to which our institution had access. Cases where the patient died were excluded. This narrowed the literature down to 35 articles. Articles focusing on patients with end stage renal disease were excluded. Cases of intrathecal baclofen overdose were also excluded. We reviewed 23 open-access case reports with a total of 31 patients describing acute oral baclofen overdose. See table 1 of the included journals at the end of the discussion section. Overdose of baclofen has been reported in healthy adults with single oral doses as little as 150 mg1 up to 3000 mg.2 There have been cases of toxicity reported with smaller oral doses, but these occurred in either paediatric patients or adult patients with end-stage renal disease.3–6
The signs and symptoms of baclofen overdose are primarily neurological and cardiovascular. Of the 31 patients included in this review, the most common manifestations were coma (76.6%), bradycardia (46.6%), hypothermia (40.0%), hyporeflexia (40.0%), hypotonia (40.0%) and respiratory depression (36.6%). In addition to the 12 patients who demonstrated hyporeflexia, another 7 patients were described as areflexic. Few articles described if the authors were referring to deep tendon reflexes or central reflexes. There were four cases specifically describing absent gag reflex, three cases with absent corneal reflexes and one case mentioning absent pupillary reflex. It appears that baclofen toxicity impairs both deep tendon reflexes and central reflexes to some degree. There were five instances of patients developing seizures following an overdose. Interestingly, there are reports of both hypotension (16.6%) and hypertension (16.6%). It has been theorised that this may represent acute withdrawal following overdose.7 Baclofen toxicity is unique in that there have been reported cases of rapidly alternating tachycardia and bradycardia as well as hypotension and hypertension.8 The patient described in our case exhibited many of the typical signs of baclofen overdose including hypotension, bradycardia and respiratory depression. However, this patient did display some unexpected cardiac findings including the ST elevations and apical ballooning of the left ventricle. Patients who receive toxic doses intrathecally have similar presentations.9–14 Despite these grave findings, patients frequently recover fully with supportive care.15 16
Most often, gas chromatography-mass spectrometry and high-performance liquid chromatography (LCMS) are used to detect toxic levels of baclofen. Another laboratory technique, combined liquid chromatography with high-resolution mass spectrometry (LC-HRMS), is emerging which promises rapid detection of baclofen levels.17 To our knowledge, this technology has only been used in one post-mortem case of baclofen overdose.18 Both LC-MC and LC-HRMS are not readily available in many institutions, further complicating detection and thus treatment.19 Many patients continue to exhibit signs, and symptoms after serum levels decrease to therapeutic levels.20 Treatment typically consists of supportive care. Coma and respiratory depression/failure should be treated aggressively with intubation. Supportive care should be accomplished using short-acting pharmacological agents because haemodynamic fluctuations are rapid and frequent. Patients with severely impaired renal function who overdose on baclofen may have their hospital courses shortened by haemodialysis. Evidence of efficacy in patients without renal dysfunction is limited.21 22 There have been a few cases specifically addressing the use of atropine for the bradycardic and hypotensive patient with some success.1 23
Learning points
Combined liquid chromatography high-resolution mass spectrometry shows promise in rapidly detecting toxic baclofen levels; however, this is not available in many institutions.
Baclofen overdose can mimic brain death but frequently results in full recovery.
Consultation with a toxicologist or toxicology guidelines may hasten treatment.
Haemodynamic volatility requires careful and frequent re-evaluation of treatment.
Early recognition and anticipation of complications is essential for effective management of baclofen overdose, which can be life-threatening.
Ethics statements
Patient consent for publication
References
Footnotes
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms and critical revision for important intellectual content: CMD, CHY, MG. The following author gave final approval of the manuscript: SCM.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.