Prone ventilation in a pregnant patient with scrub typhus-induced acute respiratory distress syndrome

Abstract

A 23-year-old primigravida at 20 weeks of gestation presented to our hospital with undifferentiated febrile illness and severe acute respiratory distress syndrome. She was intubated in the emergency department and transferred to the intensive care unit. Initial treatment included ventilatory care, vasopressor support and broad-spectrum antibiotics. Based on a positive PCR assay for scrub typhus, she was treated with intravenous doxycycline and azithromycin. Despite reduction in fever, her oxygenation further declined. Following a risk–benefits assessment, we decided to ventilate her in prone position for 8 hours a day for three consecutive days using a checklist-based protocol. Her oxygenation indices and lung compliance markedly improved over this period, and she was extubated a day later. She was eventually discharged home after 1 week.

Background

Acute respiratory distress syndrome (ARDS) in pregnancy is among the most complex and challenging conditions managed in the intensive care unit (ICU), especially owing to the unique physiological and anatomical changes associated with pregnancy coupled with the pressure of dealing with two lives. To compound the difficulty, there are no clear evidence-based guidelines as most clinical trials exclude pregnant mothers. Herein, we describe the presentation and successful management of a pregnant woman with acute febrile illness and severe ARDS. We emphasise the role and technique of prone ventilation in addition to other strategies in managing ARDS in the ICU.

Case presentation

A 23-year-primigravida at 20 weeks gestation presented with non-specific abdominal pain and undifferentiated febrile illness to a local hospital in south India. Her initial evaluation identified thrombocytopaenia, and she was empirically treated with intravenous ceftriaxone and amoxicillin–clavulanate. She was referred to our tertiary care centre with worsening shortness of breath, non-productive cough and fever. On assessment in our emergency department, she was found to be in severe respiratory distress and marked hypoxia with an oxygen saturation of 60% on a non-rebreathing mask. She was intubated and transferred to ICU and placed on lung-protective mechanical ventilation. At admission to the ICU, she was hypotensive and required high doses of norepinephrine and vasopressin. Physical examination was unremarkable except for a doubtful eschar on the anterior abdominal wall.

Investigations

Preliminary investigations revealed leucocytosis, elevated transaminases and a positive result on Plasmodium falciparum card test. Chest radiography revealed bilateral diffuse non-homogeneous opacities. Lung ultrasonography (USG) revealed multiple B-lines with pleural irregularity and thickening. Subsequent laboratory panel (table 1) identified positive real- time PCR for scrub typhus; serological tests for malaria, influenza, dengue, chikungunya, leptospira were negative. Blood culture was sterile and procalcitonin was 1.6 ng/mL.

Table 1.

Evolution of the patient’s laboratory parameters during hospitalisation

	Day 1	Day 2	Day 5	Day 8	Day 14
Total leucocyte count (x 109/L)	31.03	22.66	26.00	24.37	14.14
Neutrophils, %	88	85	87	85	71.6
Lymphocytes, %	10	11	10.7	9	23.6
Monocytes, %	–	3	–	4	3.9
RCC (x 1012/L)	3.81	3.08	2.66	3.26	3.58
Haemoglobin, g/L	114	87	76	93	105
Platelet count (x 109/L)	187	152	223	270	295
Urea, mg/dL	11	19	31	23	19
Creatinine, mg/dL	0.32	0.38	0.16	0.10	0.31
Aspartate aminotransferase U/L	182	141	99	96	44
Alanine aminotransferase U/L	159	128	74	104	73
Total bilirubin mg/dL	1.36	0.68	0.36	0.89	0.51
Peripheral smear		RCC: normocytic, normochromic WCC- neutrophilic leucocytosis, toxic changes Parasites—not seen
Blood culture	Sterile	Sterile

RCC, red cell count; WCC, white cell count.

Treatment

After infectious diseases and neonatal specialist consultation, empirical intravenous meropenem, vancomycin, artesunate, doxycycline and oral oseltamivir were commenced. Obstetric opinion was reassuring on fetal well-being. Mechanical ventilation was continued in pressure-regulated volume control mode, targeting a tidal volume of 6 mL/kg with fraction inspired oxygen (FiO₂) 60%, positive end-expiratory pressure (PEEP) 10. Her oxygen requirement rapidly increased to 100% FiO2 with falling lung compliance up to 15 mL/cmH₂O. P/F (the ratio of partial pressure of oxygen over fraction of inspired oxygen) ratios remained below 150 despite recruitment manoeuvres, a targeted PEEP based on pressure-volume curves and sedation on fentanyl and midazolam to reduce dysynchrony. P/F ratios below 150 indicate severe ARDS. An infusion of atracurium was initiated for better ventilation and the minute ventilation was adjusted to the second-trimester target pCO₂ of 30 mm Hg. She continued to require high doses of vasopressors. After confirmation of the diagnosis of scrub typhus, all the empirical antibiotics except doxycycline were stopped and intravenous azithromycin was added considering the reduced susceptibility of some strains of Orientia tsutsugamushi to tetracyclines. On day 3, fever spikes diminished and vasopressor support could be reduced. However, the P/F ratio persisted below 150 with SpO₂ of 85%–88% on a FiO₂ of 100%. A decision to attempt prone ventilation was taken. Technical difficulties of proning and safety issues due to the gravid uterus and her haemodynamic status were discussed. In view of the potential benefits overweighing risks, and owing to her continued low P/F ratios, she was proned taking adequate precautions to avoid abdominal compression with padding below thighs, shoulders, and knees and head rings (figure 1A, B), according to our proning protocol and checklist (figure 2). Fetal heart rate (FHR) was monitored at regular intervals by USG. We found a dramatic improvement in oxygenation with P/F ratio ranging 280–440 within 8 hours of proning. There was a progressive decrease in the FiO₂, PEEP and vasopressor requirement even on reverting to supine position, though not sustained.

Figure 1.

(A, B): Patient during prone ventilation with adequate safe positioning of the gravid uterus.

Figure 2.

Checklist for prone ventilation. ABG, Arterial Blood Gas; ET, endo tracheal; ETT, Endotracheal tube; FHR, fetal heart rate; FiO2, fraction inspired oxygen; IBP, Invasive Blood Pressure; PaO2, arterial partial pressure of oxygen; RASS, Richmond Agitation Sedation score; RR, Respiratory Rate. (*) denotes specific modifications to be followed while using this check list for pregnant patients.

Daily lung USG as per our ICU protocol confirmed the decrease in the intensity of B- lines, and X-ray demonstrated diminished infiltrates. Prone ventilation was continued for another 2 days until improvement in P/F ratios was sustained for more than 4 hours in supine position as per the PROSEVA (Prone position in severe Acute Respiratory Distress trial) protocol. Daily titration of PEEP and FiO₂ based on lung mechanics was performed until she could be completely weaned off vasopressors, atracurium infusion and commenced on spontaneous mode of ventilation. After a further 24 hours, the patient was extubated and placed on oxygen supplementation (table 2). Azithromycin and doxycycline were continued for 5 and 7 days, respectively.

Table 2.

Evolution of the patient’s oxygenation and ventilation parameters during hospitalisation

Day of admission	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7
Event	At intubation	Pre proning	After 8 hours of proning	Day 2 of proning	Day 3 of proning	Without proning	Extubation
pH	7.39	7.35	7.40	7.53	7.41	7.51	7.53
PaCO2 (mmHg)	38.4	44.1	36.7	33.5	38.5	32.6	27
PaO2 (mmHg)	92.2	72	94.4	122.2	154	184.5	108
HCO3 (mmol/L)	23.0	22.6	22.5	27.8	24.0	27.3	25.2
Lactate (mmol/L)	1.4	1.65	1.35	1.52	1.16	1.13	0.9
Fio2	1.0	1.0	0.35	0.3	0.35	0.4	0.28
SO2 (%)	97.9	99.4	97.5	99	99.1	98.9	99
PaO2/FiO2	92.2	72	269.7	406	440	461.3	385
Mode	SIMV-VC	SIMV-PRVC	SIMV-PRVC	SIMV-PRVC	SIMV-PRVC	CPAP	O2 by NP @ 2 L/min
PEEP (cm H2O)	10	12	12	10	8	6	–
Plateau (cmH2O)	29	28	24	22	19	18	–

CPAP, continuous positive airway pressure; FiO₂, fraction inspired oxygen; HCO₃, bicarbonate; NP, nasal prongs; O₂, oxygen; PaO2, Arterial partial pressure of oxygen; PEEP, positive end-expiratory pressure; PRVC, pressure regulated volume controlled; SIMV, synchronised intermittent mandatory ventilation; SO₂, oxygen saturation; VC, volume controlled.

Outcome and follow-up

She had generalised muscle weakness that improved with physiotherapy in 48 hours, she was transferred out to a stepdown unit. Intermittent FHR monitoring by USG was reassuring throughout her hospital stay. She was discharged home after a further week with advice to follow up with the obstetric department.

Discussion

ARDS is an uncommon occurrence in pregnant patients with an incidence of about 16–70 per 100 000 pregnancies and is a leading cause of maternal death.¹ Pneumonia accounts for about a quarter of all ARDS in pregnancy.¹ There are multiple considerations in the management of ARDS in a pregnant patient—the need for a multidisciplinary team including intensivists, obstetricians and neonatologists, modification of oxygenation and ventilation goals, and reservations regarding proning.

Strategies to improve gas exchange in ARDS in the non-pregnant state typically include lung-protective ventilation, permissive hypercapnia and prone ventilation.^{2 3} These strategies require modification in pregnant patients for the following reasons. Starting from the first trimester, there is a 40% increase in minute ventilation, resulting in a state of compensated respiratory alkalosis. This implies the need for modifying the PaCO₂ goals while ventilating a pregnant patient (28–32 mm Hg). Excessive hypocapnia is known to reduce the uteroplacental blood flow, indicating a further need for vigilance regarding the permissible PaCO₂ levels in pregnancy. Maternal hypercapnia would result in fetal hypercapnia and acidosis.⁴ Some studies suggest that PaCO2 levels of 45–55 mm Hg appear to be reasonable in later pregnancy. However, there are no clear guidelines as to the lowest or highest permissible PaCO₂ in this population.⁵

Concerns while instituting lung-protective strategies include low tidal volume ventilation and targeting a SpO₂ 88%–95% and PaO₂ of 55–80 mm Hg. Fetal oxygen delivery is mainly determined by maternal arterial oxygen content and uteroplacental blood flow. Maternal hypoxia would result in fetoplacental vasoconstriction as the compensatory mechanisms of the maternal system are designed to protect the maternal vital organs and not the fetus.

Animal models suggest that fetal umbilical oxygenation falls from 70% to 50% when maternal SaO₂ falls from 96% to 85%. The fetus can compensate for a fall in its oxygen content up to 50% by redirection of blood flow to the brain and heart. At a fall of 75%, there is a high risk of fetal neurological damage. A maternal PaO₂ of at least 70 mm Hg is a reasonable target for oxygenation.⁶ Ventilation in the prone position is an intervention that has been proven to improve oxygenation and reduce mortality in the non-pregnant adult population.^{2 3} Similarly, the potential benefits of proning pregnant patients include a better distribution of ventilation and perfusion, decreased compression on the lungs by the heart, more caudal movement of the diaphragm, and improved cardiac output owing to the reduction in inferior vena caval compression. However, evidence in support of proning in the pregnant population is anecdotal and limited to case reports. Typically, all studies assessing the role of prone ventilation in ARDS exclude pregnant patients.⁷ To our knowledge, there are only four case reports of pregnant patients in ARDS on mechanical ventilation who were proned. Donzelli et al proned a parturient at 27 weeks of gestation who presented with severe ARDS (P/F of 64.4) following COVID-19 pneumonia for 4 days and demonstrated improvement and discharged her 33 days later from the ICU.⁸ Samanta et al described prone ventilation in a primigravida of 31 weeks gestation who was suffering from H1N1 influenza-related ARDS, who with three successive days of prone ventilation could be extubated on the 6th day of her illness.⁹ Barile et al proned a 27-week parturient with COVID-19 pneumonia and severe ARDS (P/F 75) for 16 hours on day 1 of ICU admission and were able to extubate the patient on day 15 and discharge from ICU on day 20.¹⁰ Kenn et al used this intervention in a pregnant patient of 34 weeks gestation who had sustained blunt trauma to the chest and developed ARDS.¹¹ The patient was successfully extubated on day 3 after the injury. In all these cases, as in our patient, an immediate and lasting improvement in oxygenation and gas exchange ratios was apparent, indicating proning as a highly effective intervention for pregnant patients with ARDS.

There are several challenges and concerns in using prone position in the pregnant population. Chest and pelvic bolsters have to be placed of adequate height to avoid abdominal and aortocaval compression and the ensuing hypotension. This will ensure adequate uteroplacental circulation. Trauma to dependent parts, displacement of tubes and lines along with difficulty in providing nursing care are major challenges. Careful fetal monitoring has to be done using cardiotocography depending on the gestational age or USG, as in our case. In addition to prior experience in proning, and a well-trained team, prepositioningand postpositioning checklists have to be used meticulously. At our centre, we regularly prone patients in ARDS and hence felt confident in proceeding with this treatment.

Patient’s perspective.

Translated to English

At my 6th month of pregnancy, I was febrile for 3 days, had a dry cough and gradually worsening breathlessness. When the breathlessness could not be tolerated any longer, I was taken to a local hospital where I was given a mask with oxygen but it did not improve my breathing. I felt really breathless and my chest was getting tighter. I was feeling anxious about my baby as well. I was then taken to a tertiary hospital. I do not have much memory of what happened during my stay in the ICU until I woke up 1 day and found myself comfortable and breathing on a tube in my throat. I noticed that I could not move my limbs and had weakness in all my limbs. I was given some exercises and physiotherapy. Gradually I felt my power returning back. The tube in my throat was removed the next day and my recovery from then on was uneventful. My husband and mother told me that I had been placed on my tummy to improve my breathing, but I cannot remember any of it. I am really grateful to the doctors and nurses for the care they showed me and my unborn baby during my stay in the ICU.

Learning points.

• Managing a pregnant patient with acute respiratory distress syndrome (ARDS) requires an understanding of the respiratory and circulatory physiology during pregnancy and appropriate resetting of circulatory, ventilatory and oxygenation goals.

• Prone ventilation appears to be an indispensable strategy in managing pregnant patients with severe ARDS, thereby resulting in rapid improvement in oxygenation.

• Awareness of the risks involved, a well-trained team and check-list-based protocols are essential for successful patient management.