Post-Diuretic Pulmonary Edema A Case Report CURRENT STATUS: POSTED

Background Post-diuretic pulmonary edema(PDPE)is a special type of acute pulmonary edema, results from rapid blood volume loss caused by diuretics. Inappropriate administration of diuretics and inotropic agent, which is mainstay of treatment of pulmonary edema Classically, might have been a critical mistake in PDPE.Maintaining appropriate volume status and beta receptor blockers is the key to reversing the progress of PDPE. However,this condition remains unfamiliar to the medical community, making it an underdiagnosed and underreported condition. Case representation A 71-year-old patient who initially was diagnosed to have acute respiratory distress syndrome (ADRS) in intensive care unit (ICU) but got further dyspnea after rapid volume depletion. Point of care ultrasound (POCUS) examination showed worsened pulmonary edema with inferior vena cava collapsed during inspiratory period and a small but hyperdynamic left ventricular(LV). The patient subsequently improved with fluid, beta blocker, increased sedation, and paralysis. Conclusion We first put forward the concept of post-diuretic pulmonary edema,in order to remind medical staff to pay attention to this type of pulmonary edema and understand its pathophysiological mechanism.


Abstract
Background Post-diuretic pulmonary edema(PDPE)is a special type of acute pulmonary edema, results from rapid blood volume loss caused by diuretics. Inappropriate administration of diuretics and inotropic agent, which is mainstay of treatment of pulmonary edema Classically, might have been a critical mistake in PDPE.Maintaining appropriate volume status and beta receptor blockers is the key to reversing the progress of PDPE. However,this condition remains unfamiliar to the medical community, making it an underdiagnosed and underreported condition. Case representation A 71-year-old patient who initially was diagnosed to have acute respiratory distress syndrome (ADRS) in intensive care unit (ICU) but got further dyspnea after rapid volume depletion. Point of care ultrasound (POCUS) examination showed worsened pulmonary edema with inferior vena cava collapsed during inspiratory period and a small but hyperdynamic left ventricular(LV). The patient subsequently improved with fluid, beta blocker, increased sedation, and paralysis. Conclusion We first put forward the concept of post-diuretic pulmonary edema,in order to remind medical staff to pay attention to this type of pulmonary edema and understand its pathophysiological mechanism. Case Presentation 3 A 71-year-old male presented to our hospital because of an incidentally discovered subpleural tubercle on right inferior lobe. Biopsy showed non-small cell lung carcinoma and had a right lower lobectomy under general anesthesia to remove the lesion. On the 5th day postoperative the patient was noted to be short of breath and dyspneic. On examination his heart rate was 122 beats per minute, respiratory rate 30 breaths per minute, and oxygen saturation 86 to 90% on 10 liters of oxygen by face mask. He was intubated and transferred to the ICU.
Upon ICU arrival, the patient was sedated with propofol, remifentanil and mechanically ventilated using volume control mode, with low tidal volumes (6 ml per kilogram of predicted body weight), positive end-expiratory pressure PEEP of 7cmH 2 O, respiratory rate of 20 breaths per minute and the fraction of inspired oxygen FiO 2 of 100%. With these settings, the patient continued to have respiratory distress. Physical examination revealed bilateral lung moist rale, normal heart sounds, and yellowish, viscous sputum in the endotracheal tube. His chest radiograph revealed bilateral diffuse and heterogeneous opacities (Fig.1a).
Meeting the criteria of severe ADRS, he was treated with analgesia deep sedation neuromuscular blocking agents (NMBAs) and fluid restrictive management strategy. His respiratory status improved in the ensuing 5 days. Anteroposterior chest radiograph showed decreased pulmonary opacities (Fig.1b). Mechanical ventilation was weaned to a implying that there is underlying LV diastolic dysfunction [1] . Putting this all together, this shows that the left atrial pressure was elevated, and the LV filling was impaired. At this time, lung ultrasound evaluation showed increased B lines in both lungs and no A lines. This is consistent with a substantially increased amount of extra vascular lung water, 5 despite diuresis. (Fig.1d) Based on the result of the POCUS evaluation the low cardiac preload due to the rapid volume loss resulted in hyperdynamic LV contractions. This lead to increased resistance of LV ejection during systole and difficulty with LV filling during diastole. The increased LV end-diastolic pressure and left atrial pressure were then transmitted to the pulmonary capillaries and pushed fluid out of the vessels, which ultimate resulted in worsening of the patient's pulmonary edema. Although the pulmonary arterial wedge pressure estimated from E/e' was not high enough to induce hydrostatic pulmonary edema, the effect of hydrostatic pressure on the pulmonary edema was amplified by the high pulmonary capillary permeability due to ARDS and pneumonia. Eventually, the patient had worsening pulmonary edema and worsening respiratory distress then which triggered negative pressure pulmonary edema (NPPE) attributed to the marked negative intrapleural pressure [2][3][4] .
If this mechanism is not recognized, then the typicaly treatment would involve extra diuresis and possibly vasodilators, inotropic agents, and increased mechanical ventilation support. Unfortunately, these treatment would result in worsening of the patient's suffer pulmonary edema.

Treatment
After determining that the patient required fluid despite pulmonary edema, the patient received fluid therapy, beta-blocker (intravenous esmolol), and increased sedation to mitigate LV stress. In order to eliminate the side effects of deep spontaneous breath, the patient was deeply sedated and paralyzed with NMBAs (cisatracurium besylate, 5mg per hour). After 2 days, the fluid balance was positive about 1390ml. Meanwhile the patient was stabilized again on mechanical ventilation requiring an FiO 2 of 45%, respiratory rate 6 of 20 breaths per minute and PS of 12cmH 2 O with PEEP of 6cmH 2 O. Repeat POCUS showed the LV cavity enlarged and IVC diameter increased to 2.1cm (Fig.2b, video in supplementary file 2), with a laminar LVOT blood flow in systole (Fig.3a right panel) and a laminar LV cavity blood flow from base to apex in diastole (Fig.3c right panel) (video in supplementary file 4). The LVOT pressure gradient decreased to 9.0mmHg in systole ( Fig.3b right panel) and the LV E/e'ratio decreased to 9. This indicated that the left atrial pressure decreased. Lung ultrasound examination showed decreased B lines compared to 48 hours before and A lines reappeared in both lungs. (Fig.1e)

Discussion
Diuresis is the most often used method for treating pulmonary edema. On the contrary, we first put forward the concept of post-diuretic pulmonary edema PDPE .
Pulmonary edema results from increased hydrostatic pressure and increased permeability of the vessels [5] . The general consensus in treating pulmonary edema is a restrictive fluid strategy in conjunction with diuresis. However if diuresis is too quick, hypovolemia will occur and result in the heart and the lung working harder to increase oxygen delivery.
This will lead to a hyperdynamic LV and increased tidal volumes during spontaneous breathing. Fig.4 The hyperdynamic LV will increase LV end-diastolic pressures due to the elevated resistance of LV ejection in systole and LV filling in diastole. This increased resistance is transmitted to the pulmonary capillaries and will increase pulmonary capillary hydrostatic pressure which will worsen hydrostatic pulmonary edema. Particularly, this outcome can be aggravated in the condition of high pulmonary capillary permeability.
Deep and quick breaths from pulmonary edema will decrease thoracic pressure even to negative, which will worsen hydrostatic pulmonary edema by increasing pulmonary 7 capillary hydrostatic pressure. Firstly, the negative thoracic pressure will increase RV output by drawing more venous blood return to RV [3 4 6] and will decrease LV output by elevating LV transmural pressure contributing to LV afterload increasing [7] . Together these two elements lead to pulmonary capillary hydrostatic pressure increased. Secondly, the negative thoracic pressure will further increase trans-pulmonary capillary pressure.
The combination of all these elements in our patient resulted in worsening of hydrostatic pulmonary edema.
Negative thoracic pressure will also worsen pulmonary permeability edema by increasing transpulmonary pressure which will further exacerbate lung injury.
Putting this all together, our patient got worsening of pulmonary edema, despite volume depletion --Post-Diuretic Pulmonary Edema PDPE).

Consent for publication
Written informed consent was obtained from the patient for publication of this article and any accompanying images and videos.

Availability of data and materials
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Competing interests
The authors declare that they have no competing interests.