Severe tachypnoea and dyspnoea due to physiological hyperventilation in pregnancy

Introduction

Hyperventilation and dyspnoea are common in pregnancy, most symptoms occurring due to physiological adaptations in the setting of rising progesterone. Progesterone-induced hyperventilation ensures the increasing metabolic demands of pregnancy are met. Importantly, physiological hyperventilation and dyspnoea in pregnancy are associated with an increase in tidal volume, while the respiratory rate remains unchanged and symptoms are not typically severe enough to impact on quality of life. We report a case of severe physiological hyperventilation in pregnancy with profound dyspnoea, tachypnoea and presyncope with associated severe chronic respiratory alkalosis with metabolic compensation.

Case presentation

A 35-year-old woman in her fourth pregnancy presented at 18 weeks of gestation gestational age with worsening dyspnoea, presyncope, upper limb paraesthesia and fatigue. She had no significant medical history, was not taking any regular medications, is a life-long non-smoker and denied any recreational drug or alcohol use. There was no known family history of cardiac, respiratory or haematological disorders.

Prior to presentation, her pregnancy had been uneventful, and moreover her previous three pregnancies and vaginal deliveries were uncomplicated. The patient lived at home with her husband and, three young children, and lived an active lifestyle running approximately 14 km three times weekly pre-pregnancy. She reported no current or past history of mood disturbance or social stressors.

The patient initially presented at 18 weeks of gestation gestational age reporting increasing dyspnoea with reduced exercise tolerance to approximately 100 m. By week 28, the patient was reporting severe dyspnoea with reduced exercise tolerance to 20 m, presyncope, bilateral hand paraesthesia, and only able to speak in short sentences. There was no associated chest pain, palpitations, cough, haemoptysis or altered mental state.

On examination, she appeared slim with a normal body mass index (BMI) at 20 kg/m². Examination revealed an increased respiratory rate of 24 breaths/min, increased work of breathing with use of accessory muscles of respiration and difficulty in speaking in full sentences. Oxygen saturations were 100% on room air, blood pressure was 116/66 mm Hg, and pulse rate 80 beats/min. Head and neck examinations were unremarkable. On cardiorespiratory examination, an ejection systolic murmur was noted and normal vesicular breath sounds. On abdominal palpation, the symphysis-fundal height was appropriate for dates, the fetus was in the breech position, growth was on the 50th percentile with a normal amniotic fluid index and umbilical artery Doppler.

Investigations

Arterial blood gas analysis demonstrated a severe chronic respiratory alkalosis with partial metabolic compensation (Table 1). Full blood count was normal apart from a mild neutrophilia (8.4 × 10⁹/l). Biochemistry revealed a persistently reduced bicarbonate throughout pregnancy secondary to partial metabolic compensation for the respiratory alkalosis. Renal function, liver function and electrolytes all remained within normal range. Iron studies, thyroid function and autoimmune screen were all normal. Urine was unremarkable with no proteinuria or bacteriuria. Progesterone levels measured during the third trimester were consistent with expected values at 360.1 nmol/l.

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Table 1.

Arterial blood gas.

Parameter	Week 33	Week 34	Week 37	Normal range
pH	7.57	7.63	7.51	7.35–7.45
PCO2 (mm Hg)	18	14	19	35–45
PO2 (mm Hg)	108	106	115	83–108
Base excess	−3.4	−4.3	−5.6	−3.0 to + 3.0
HCO3 (mmol/l)	17	15	15	22–28

Extensive further investigations were undertaken to determine the aetiology of the severe hyperventilation and tachypnoea. Transthoracic echocardiogram showed mild biventricular dilatation equivalent to expected values during normal pregnancy with normal systolic function and a small intra-atrial shunt, likely a small secundum atrial septal defect (ASD), which was hemodynamically not significant.

CT pulmonary angiogram was negative for pulmonary embolus, demonstrated clear lungs and pleural spaces with no pulmonary infiltrates, no pleural effusion or pericardial effusion. Bilateral lower limb Doppler ultrasounds found no evidence of deep vein thrombosis. MRI brain demonstrated no intracranial abnormality, and spirometry was within normal limits. A sleep study was undertaken due to the patient reporting increased snoring throughout this pregnancy with associated increased daytime somnolence. The sleep study demonstrated no evidence of obstructive sleep apnoea.

Treatment

After extensive investigations without identification of an underlying acute aetiology, the patient was diagnosed with severe physiological hyperventilation of pregnancy. Given the significant symptoms, the patient was trialled on a short-acting benzodiazepine, oxazepam 3.75 mg, at 34 weeks of gestation. The benzodiazepine was associated with a transient mild improvement in symptoms; however, no improvement was noted in biochemical markers, namely, the patient's persistent respiratory alkalosis. Table 1 demonstrates the patient's arterial blood gas results post-commencement of benzodiazepines in week 34 of gestation, compared to earlier in pregnancy without use of benzodiazepines.

Significant discussions took place with the patient regarding the risk and benefits associated with using benzodiazepines in pregnancy given their association with preterm delivery, low birth weight and neonatal sedation.^1,2 The patient decided not to continue benzodiazepines during her pregnancy. Upon cessation of the oxazepam, the patient's hyperventilation and associated symptoms returned to predose levels.

The patient continued to deny any mood changes or stressors throughout the entirety of the pregnancy; however, given the ongoing burden of symptoms, a joint decision between patient and physician was made to commence citalopram 10 mg daily at 34 weeks of gestation. The aim of citalopram was to alleviate any anxiety associated with severe tachypnoea and dyspnoea. She remained on citalopram for the remainder of her pregnancy with mild subjective improvement in symptoms, including increased exercise tolerance to 50 m. Objective measurements demonstrating improvements in hyperventilation were not observed. The patient remained tachypnoeic with a persistent respiratory alkalosis.

Outcome

The patient's symptoms persisted until induction of labour and uncomplicated vaginal delivery of a liveborn singleton at 37 weeks of gestation. One month post-delivery, the patient’s tachypnoea largely resolved with only very mild tachypnoea on walking long distances. Her respiratory alkalosis resolved, and progesterone levels reduced to pre-pregnancy levels at 1.8 nmol/l.

Discussion

Hyperventilation and dyspnoea are common during pregnancy. Most commonly, it occurs secondary to physiological adaptations. Resting minute ventilation increases by approximately 40% towards the end of the third trimester. ³ Importantly, this increase in minute ventilation is associated with a higher tidal volume, while respiratory rate remains unchanged. ⁴ Interestingly, our patient had a persistent tachypnoea ranging from 22 to 26 breaths/min from 18 weeks of gestation to term. We were unable to find any similar reports of sustained tachypnoea during pregnancy.

Progesterone-induced hyperventilation is considered a key driver in increasing ventilation during pregnancy to meet increased metabolic demands. ⁵ Progesterone increases the sensitivity of the respiratory centre to carbon dioxide via an oestrogen-dependent progesterone-receptor-mediated facilitation of central neural mechanisms, independent of hydrogen and the respiratory chemoreflexes.^6,7

Jenson et al. were the first to employ an iso-hyperoxic rebreathing procedure in a longitudinal study of 35 pregnant healthy women to elicit physiological ventilation changes in normal pregnancy. ⁶ They demonstrated hyperventilation with associated respiratory alkalosis was secondary to more complex interactions than simply hormonal-induced changes. They found a complex interplay between acid–base balance, wakefulness driving breathing, increased metabolism and decreased cerebral blood flow. ⁶ This research in combination with our case demonstrates, while there have been advances in the understanding of respiratory adaptations in pregnancy, the complete underlying pathophysiology is not entirely clear.

There is limited literature available on the potential outcomes associated with hypocapnia secondary to hyperventilation in pregnancy. While the effects of maternal PCO₂ have been examined in multiple animal studies, studies in humans are severely lacking. Two previous publications found reducing maternal PCO₂ has no significant effects on the fetal heart rate.^8,9 Further studies are required to determine the effects of maternal hypocapnia on placental and fetal cerebral blood flow.^8,9

Dyspnoea and hyperventilation are closely interlinked given increased respiratory drive strongly correlates with an individual's perception of dyspnoea. ³ However, it is vital in patients presenting with tachypnoea and dyspnoea in pregnancy that underlying pathology be excluded. In our case, significant investigations were undertaken which excluded common differential diagnosis of tachypnoea and dyspnoea, such as pulmonary embolism, heart or lung disease, anaemia, endocrine disorders and those specific to pregnancy including, preeclampsia and peripartum cardiomyopathy. Given we were unable to identify an underlying pathology responsible for our patient's tachypnoea and dyspnoea, we postulate her symptoms were secondary to an exaggerated physiological hyperventilation of pregnancy.

There is limited literature pertaining to treatment of physiological hyperventilation and dyspnoea in pregnancy. In our case, a selective-serotonin reuptake inhibitor and benzodiazepine were trialled with limited effect. This case highlights a rare case of severe tachypnoea and dyspnoea secondary to exaggerated physiological hyperventilation in pregnancy. Since physiological dyspnoea in pregnancy remains a diagnosis of exclusion, it remains vital to ensure underlying pathological causes of dyspnoea is excluded.