A Perfect Storm: Pulmonary Edema Following Misoprostol Administration in the Midst of Sepsis, Pneumonia, and Retained Pregnancy: A Rare Case Report

ABSTRACT

Pulmonary edema is a rare but serious event that can occur in critically ill obstetric patients with multiple comorbidities. This case describes its occurrence following misoprostol administration in a highly vulnerable patient with sepsis, preeclampsia, and intrauterine fetal demise. While a temporal association was observed, causation cannot be definitively established. This report highlights the importance of vigilant monitoring and readiness for advanced respiratory support when using uterotonics in high‐risk, destabilized patients. It is crucial to emphasize that misoprostol remains a safe and lifesaving medication for the vast majority of obstetric patients, and this unique case should not deter its essential use.

1. Introduction

Misoprostol, a synthetic prostaglandin E1 analogue, has revolutionized obstetric care due to its cost‐effectiveness, stability, and wide range of applications, including medical abortion, labor induction, and postpartum hemorrhage management [1, 2]. The drug's pharmacokinetics demonstrate significant route‐dependent variability, with vaginal administration providing sustained uterine activity but exhibiting greater interindividual absorption differences compared to oral or sublingual routes [3, 4]. While most adverse effects are mild (e.g., fever, chills, and diarrhea), serious complications such as uterine rupture, coronary artery spasm, and non‐cardiogenic pulmonary edema have been reported, albeit rarely [5].

The development of pulmonary edema following misoprostol administration represents a particularly severe and rare adverse event. Current literature suggests multiple potential mechanisms, including prostaglandin‐induced increase in vascular permeability, systemic vasodilation leading to fluid redistribution, and possible myocardial dysfunction. Prostaglandin E2 (PGE2) analogues such as sulprostone have been associated with cases of pulmonary edema; however, there are no documented reports in the literature linking misoprostol to this adverse effect [6, 7]. These effects may be potentiated in high‐risk obstetric patients with underlying sepsis, hypertensive disorders, or compromised cardiovascular function [8, 9]. We present a case of acute pulmonary edema following vaginal misoprostol administration in a septic patient with preeclampsia and intrauterine fetal demise, contributing to the limited but important body of evidence regarding this life‐threatening complication. This report aims to underscore the need for careful patient selection, dose consideration, and hemodynamic monitoring when using misoprostol in critically ill obstetric patients, while acknowledging the difficulty in establishing direct causation and the exceptional nature of this clinical scenario.

2. Case Report

2.1. Case History/Examinations

A 34‐year‐old G2A1 woman at 13 + 3 weeks gestation presented with a 2‐day history of low‐grade fever, abdominal pain, and vomiting. Her medical history included chronic hypertension (on amlodipine) and hypothyroidism (on levothyroxine), with no known cardiopulmonary disease. On admission, she was tachycardic (HR 145 bpm), hypertensive (BP 160/110 mmHg), and tachypneic (RR 35/min), with 94% SpO₂ on room air. Obstetric examination revealed uterine tenderness, and ultrasound confirmed intrauterine fetal demise (IUFD). Laboratory findings showed anemia (Hb 8.5 g/dL), thrombocytopenia (85,000/μL), elevated liver enzymes (AST 145 IU/L, ALT 132 IU/L), acute kidney injury (creatinine 1.8 mg/dL), and coagulopathy (INR 1.5). Blood cultures grew gram‐negative rods, and chest X‐ray demonstrated bilateral pulmonary infiltrates (Figure 1), leading to diagnoses of sepsis (source being retained conceptus confirmed by histopathology), pneumonia, HELLP syndrome, and preeclampsia superimposed on chronic hypertension.

FIGURE 1.

Chest X‐ray shows features suggestive of pulmonary edema including Kerley A (black arrow) and Kerley B (green arrow).

3. Methods

The patient was admitted to the ICU for aggressive management, including broad‐spectrum antibiotics, labetalol to achieve BP goal of < 140/90 mmHg, thromboprophylaxis with the aid of sequential compression device, and supportive care. Despite treatment, she remained febrile (peak 102°F) with persistent tachycardia (heart rate in the range of 145–161 bpm), tachypnea (respiratory rate in the range of 23–32/min) and laboured breathing over 72 h. On day 4, 600 μg vaginal misoprostol was administered to evacuate the retained conceptus. Within 1 h, she developed acute hypoxemic respiratory failure (SpO₂ 78%), with bilateral crackles and radiographic evidence of pulmonary edema (Figure 1). Urgent ABG was done which showed metabolic acidosis, raised lactate level upto 4 mmol/L and PO₂/FiO₂ ratio only 80 on 100% FiO₂. 2D‐echocardiography was also done on bedside to rule out cardiogenic cause of pulmonary edema. She underwent rapid‐sequence intubation and was mechanically ventilated with volume‐controlled settings (FiO₂ 100%, PEEP 8 cmH₂O, tidal volume 400 mL).

Diuresis with IV furosemide (40 mg) and conservative fluid strategies were initiated alongside lung‐protective ventilation. Strict input/output monitoring done in order to avoid the risk of fluid overload. Repeated dose of 600 μg vaginal misoprostol was administered to evacuate the retained conceptus since it was not evacuated completely. Same phenomena was seen as previous episode which included pink frothy sputum, bilateral crackles, multiple B‐lines on ultrasonography and radiological evidence of pulmonary edema. Again, patient was managed as done previously. Serial arterial blood gases guided ventilator adjustments, with gradual improvement in oxygenation over 48 h. Uterine evacuation was performed under fentanyl and midazolam sedation for sepsis source control, and antibiotics were tailored to culture sensitivities.

4. Conclusion and Results

Post‐stabilization, the fetus was expelled within 12 h. The patient was successfully extubated after 48 h of ventilatory support, with resolution of pulmonary edema on repeat imaging. The patient was discharged on day 12 with plans for outpatient hypertension and thyroid management. At 3‐week follow‐up, she remained clinically stable without residual cardiopulmonary or obstetric complications. This case describes a strong temporal association between misoprostol administration and acute pulmonary edema in a critically ill obstetric patient. It emphasizes the need for vigilant monitoring and immediate access to advanced life support in such high‐risk settings, while acknowledging that the contribution of the patient's underlying critical illness to this event cannot be ruled out.

5. Discussion

The development of pulmonary edema soon after misoprostol administration is an exceptionally rare event that warrants careful consideration. The underlying mechanisms could potentially involve prostaglandin‐mediated increases in vascular permeability coupled with significant hemodynamic instability from preexisting conditions like sepsis and preeclampsia [1]. In this unique case, the combination of sepsis, pneumonia, and hypertensive disorders created a clinical scenario where the administration of misoprostol was followed by acute pulmonary compromise. The temporal relationship between drug administration and symptom onset is notable. However, it is critical to interpret this association with caution. Given the patient's profound and prolonged critical illness, it is not possible to definitively establish misoprostol as the sole causative factor. The pulmonary edema could also be attributed to the natural progression of her sepsis, severe preeclampsia, or underlying renal impairment. This diagnostic challenge underscores the importance of maintaining a high index of suspicion for various etiologies, including medication‐related effects, when managing complex patients with multiple competing diagnoses.

This case carries significant implications for obstetric practice in exceptionally high‐risk clinical scenarios. It is paramount to state unequivocally that misoprostol remains a cornerstone of obstetric care and a lifesaving medication for the vast majority of patients worldwide. The intent of this report is not to deter its essential use but to highlight a potential for complication in a uniquely vulnerable population. While misoprostol is overwhelmingly safe, its use in critically ill, destabilized patients with sepsis, severe hypertensive disorders, or significant pulmonary/renal involvement requires extreme caution and meticulous individualized risk–benefit assessment. The potential for rapid clinical deterioration in such patients necessitates that administration occurs only in settings where immediate advanced respiratory and life support is available. These findings contribute to the understanding of patient safety in complex obstetric cases and reinforce the need for heightened vigilance and tailored management plans for the most severely ill patients. Ultimately, this case serves as an important reminder that in patients with multiple severe comorbidities, clinical decompensation can have multifactorial causes, and even commonly used medications may be associated with rare adverse events in these specific contexts.

Author Contributions

Rahul Kumar Chaudhary: conceptualization, writing – original draft, writing – review and editing. Prajwal Bista: conceptualization. Lalit Kumar Rajbanshi: conceptualization. Deepak Poudel: conceptualization. Kumud Pyakurel: conceptualization.

Disclosure

Disclaimer: The content of this case report is original, with the English language rephrasing completed using Deepseek.com.

Consent

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Chaudhary R. K., Rajbanshi L. K., Poudel D., Pyakurel K., and Bista P., “A Perfect Storm: Pulmonary Edema Following Misoprostol Administration in the Midst of Sepsis, Pneumonia, and Retained Pregnancy: A Rare Case Report,” Clinical Case Reports 13, no. 11 (2025): e71377, 10.1002/ccr3.71377.

Data Availability Statement

Data will be provided by the corresponding author upon reasonable request. Images are uploaded in the separate files.