Severe Intraabdominal Hypertension in Critically Ill COVID-19 Patients With Acute Kidney Injury

Abstract

COVID-19-induced acute respiratory distress syndrome has been described as an atypical form of the syndrome, notably by showing well-preserved pulmonary compliance in a large subset of patients.1Marini J.J. Gattinoni L. Management of COVID-19 respiratory distress.JAMA. 2020; 323: 2329-2330Crossref PubMed Scopus (616) Google Scholar,2Gattinoni L. Coppola S. Cressoni M. Busana M. Rossi S. Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome.Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (838) Google Scholar Beyond the respiratory presentation of the disease, acute kidney injury (AKI) occurs in up to 25% of COVID-19 critically ill patients and is independently associated with a higher mortality rate, especially when renal replacement therapy (RRT) is required.3Chaibi K. Dao M. Pham T. et al.Severe acute kidney injury in patients with COVID-19 and acute respiratory distress syndrome.Am J Respir Crit Care Med. 2020; 202: 1299-1301Crossref PubMed Scopus (19) Google Scholar Clinicians’ choices in both the ventilation strategy and the fluid stewardship of these patients could directly impact renal function, notably by changing intraabdominal pressure (IAP).4Reintam Blaser A. Regli A. De Keulenaer B. et al.Incidence, risk factors, and outcomes of intra-abdominal hypertension in critically ill patients: a prospective multicenter study (IROI Study).Crit Care Med. 2019; 47: 535-542Crossref PubMed Scopus (84) Google Scholar The use of mechanical ventilation with high positive end-expiratory pressure (PEEP) levels as well as fluid overload have been well demonstrated to be associated with intraabdominal hypertension (IAH) in ICU patients.5Kirkpatrick A.W. Roberts D.J. De Waele J. et al.Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome.Intensive Care Med. 2013; 39: 1190-1206Crossref PubMed Scopus (814) Google Scholar We aimed to assess IAH occurrence at the time of AKI development as well as IAP variation while changing fluid load and PEEP level in critically ill COVID-19 patients. We screened all adult patients hospitalized in the ICU at the University Hospital of Reims (Northeastern France) between March 15 and May 15, 2020, with a diagnosis of COVID-19-induced ARDS requiring mechanical ventilation, who developed AKI, defined as stage 3 according to the Kidney Disease Improving Global Outcomes classification. Clinical data of all included patients were obtained by reviewing clinical charts and nursing records. Because of the well-known association between IAH and AKI, IAP was systematically monitored by intravesical pressure measurement with the Unometer Abdo-Pressure device every 8 hours in all patients developing AKI in our ICU according to a local protocol.6Dupont V. Debrumetz A. Leguillou A. et al.Intra-abdominal hypertension in early post-kidney transplantation period is associated with impaired graft function.Nephrol Dial Transplant. 2020; 35: 1619-1628Crossref PubMed Scopus (5) Google Scholar IAH was defined according to the World Society of Abdominal Compartment Syndrome as an increase in IAP above 12 mm Hg for more than 24 hours and graded as following: grade I, 12 to 15 mm Hg; grade II, 16 to 20 mm Hg; grade III, 21 to 25 mm Hg; grade IV, >25 mm Hg. IAH grades III to IV were considered as severe.5Kirkpatrick A.W. Roberts D.J. De Waele J. et al.Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome.Intensive Care Med. 2013; 39: 1190-1206Crossref PubMed Scopus (814) Google Scholar Management of IAH patients in our ICU included, when possible, a fluid-restrictive strategy and a decrease in PEEP level. Quantitative and qualitative data are reported as median [interquartile range] and number (percentage), and compared with Mann-Whitney test and χ2 test with OR and 95% CI, respectively. P < .05 was considered statistically significant. Ninety-one COVID-19 patients were admitted to our ICU during the study period, and 64 (70.3%) required mechanical ventilation. Among the ventilated patients (median age, 69 [15.2] years; male, 51.6%), 20 (31.2%) developed stage 3 AKI during the ICU stay, all within the first 72 hours after admission (three patients were excluded because of missing data). Compared with non-AKI patients, patients with AKI were most likely to be men (88.2% vs 40.9%; OR = 10.8; 95% CI, 2.5-46.7; P < .01) and showed higher BMI (32.0 [6.7] vs 27.8 [6.8]; P = .03). At the time of AKI development, all 17 (100%) included patients who developed AKI exhibited IAH with a median IAP of 23 (8) cm H2O. Eleven (64.7%) had severe IAH and tended to show higher rates of both RRT requirement (54.6% vs 16.7%; OR = 6.0; 95% CI, 0.7-50.6; P = .13) and in-ICU mortality (72.7% vs 50%; OR = 2.7; 95% CI, 0.4-18.5; P = .35) compared with patients with nonsevere IAH (Table 1). At the time of AKI development, all included patients showed relatively preserved pulmonary compliance (44 [10] mL/cm H2O) and were treated with high PEEP levels (12 [4] cm H2O) and highly positive 24-hour fluid balance (2,070 [1,975] mL), whereas biochemical urinary analyses were mostly suggestive of prerenal aggression (Table 1). Our local protocol, including a decrease in fluid load (199.5 [1,962.8] vs 2,070 [1,975] mL; P < .01) and PEEP levels (10 [3] vs 12 [4] cm H2O; P < .01), was associated with a decrease in IAP (13.5 [4] vs 23.0 [8] mm Hg; P < .01) and an increase in daily diuresis (1,510 [1,010] vs 925 [528] mL; P < .01) within 5 days (Fig 1).Table 1Characteristics of the 17 Ventilated Patients With COVID-19 Developing Acute Kidney Injury in the ICUVariablesAll Patients With AKIN = 17IAH Grade I-IIn = 6IAH Grade III-IVn = 11Demographic data Age, y70, 973, 769, 10 Men, No. (%)15 (88.2)6 (100)9 (81.8) Hypertension, No. (%)13 (76.5)4 (66.7)9 (81.8) Diabetes, No. (%)7 (41.2)3 (50)4 (36.4) BMI32, 731, 332, 7 CKD, No. (%)3 (17.6)1 (16.7)2 (18.2) Baseline creatinine level, μmol/L78, 3481, 2078, 35 RAAS blocker, No. (%)9 (52.9)4 (66.7)5 (45.5) Corticosteroid, No. (%)6 (35.3)2 (33.3)4 (36.4) Bacterial coinfection, No. (%)7 (41.2)3 (50)4 (36.4)Acute kidney injury Days from ICU admission, d2, 12, 13, 1 Proteinuria, mg/mmolCreatinuria48, 5240, 2863, 57 Urine sodium/potassium ratio <19 (52.9)3 (50)6 (54.5) Urine/plasma creatinine ratio >3015 (88.2)5 (83.3)10 (90.9) Urine/plasma urea ratio >1013 (76.5)4 (66.7)9 (81.8) Fractional excretion of urea <35%15 (88.2)5 (83.3)10 (90.1)Respiratory parameters Compliance, mL/cm H2O44, 1045, 1144, 7 PEEP, cm H2O12, 411, 412, 4 ECMO, No. (%)3 (17.6)1 (16.7)2 (18.2)Hemodynamic parameters 24-Hour fluid balance2070, 19751945, 18672070, 2075 Norepinephrine > 0.25 μg/kg/min14 (82.3)5 (83.3)9 (81.8)Outcome Renal replacement therapy, No. (%)7 (41.2)1 (16.7)6 (54.6) Mesenteric ischemia, No. (%)1 (5.9)01 (9.0) ICU mortality, No. (%)11 (64.7)3 (50)8 (72.7)Categorical and continuous variables are presented as No. (%) and as median with interquartile range, respectively. CKD = chronic kidney disease; ECMO = extracorporeal membrane oxygenation; IAH = intraabdominal hypertension; RAAS = renin-angiotensin-aldosterone system. Open table in a new tab Categorical and continuous variables are presented as No. (%) and as median with interquartile range, respectively. CKD = chronic kidney disease; ECMO = extracorporeal membrane oxygenation; IAH = intraabdominal hypertension; RAAS = renin-angiotensin-aldosterone system. The pathophysiology of COVID-19-related AKI remains incompletely elucidated and is probably multifactorial.7Gabarre P. Dumas G. Dupont T. Darmon M. Azoulay E. Zafrani L. Acute kidney injury in critically ill patients with COVID-19.Intensive Care Med. 2020; 46: 1339-1348Crossref PubMed Scopus (259) Google Scholar The independent association between elevated IAP and renal function impairment has been well established and is mainly explained by renal venous congestion, which impairs glomerular filtration by decreasing renal plasma flow.8Mohmand H. Goldfarb S. Renal dysfunction associated with intra-abdominal hypertension and the abdominal compartment syndrome: table 1.JASN. 2011; 22: 615-621Crossref Scopus (133) Google Scholar As previously reported, obesity, which concerns a large subset of critically ill patients with COVID-19, is an independent risk factor of IAH.6Dupont V. Debrumetz A. Leguillou A. et al.Intra-abdominal hypertension in early post-kidney transplantation period is associated with impaired graft function.Nephrol Dial Transplant. 2020; 35: 1619-1628Crossref PubMed Scopus (5) Google Scholar Describing a homogeneous population of ventilated patients with COVID-19 who developed severe AKI during ICU stay, we found that all of them had IAH at the time of AKI development. Additionally, although we did not find IAH grades III to IV to be significantly associated with worse outcomes, which might be attributable at least in part to our small sample size, patients with severe IAH tended to show higher rates of RRT and in-ICU death. Furthermore, we found that IAP decreased significantly in univariate analysis while decreasing fluid load and PEEP levels (both well-known IAH risk factors). The use of high PEEP level in patients with almost normal compliance has been widely criticized because it might increase transpulmonary pressures and decrease venous return without improving oxygenation.1Marini J.J. Gattinoni L. Management of COVID-19 respiratory distress.JAMA. 2020; 323: 2329-2330Crossref PubMed Scopus (616) Google Scholar As PEEP adjustments are transmitted to the abdomen, the use of high PEEP has also been reported to promote IAH in patients under mechanical ventilation.4Reintam Blaser A. Regli A. De Keulenaer B. et al.Incidence, risk factors, and outcomes of intra-abdominal hypertension in critically ill patients: a prospective multicenter study (IROI Study).Crit Care Med. 2019; 47: 535-542Crossref PubMed Scopus (84) Google Scholar,5Kirkpatrick A.W. Roberts D.J. De Waele J. et al.Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome.Intensive Care Med. 2013; 39: 1190-1206Crossref PubMed Scopus (814) Google Scholar A liberal fluid therapy strategy might promote the development of visceral edema as well as right-sided heart failure, thus contributing to IAH.9Doyen D. Dupland P. Morand L. et al.Characteristics of cardiac injury in critically ill patients with coronavirus disease 2019..Chest. 2021; 159: 1974-1985Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Thus, the optimal fluid and respiratory stewardship remains to be established by prospective studies in COVID-19 patients with preserved pulmonary compliance to avoid the adverse effects of either underhydration or overhydration and positive pressure ventilation on kidney function in this setting.10Ostermann M. Liu K. Kashani K. Fluid management in acute kidney injury.Chest. 2019; 156: 594-603Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Despite the inherent limitation of its retrospective design, and small sample size, our study is the first to highlight the high frequency of severe IAH in patients with COVID-19 developing AKI. Although the clinical benefit of IAH prevention/treatment in terms of renal function remains to be established by interventional studies, bedside clinicians should be aware of IAH importance in critically ill patients with COVID-19 and AKI. Future larger studies are needed to prospectively assess this issue to improve outcomes, notably in ventilated patients with COVID-19. ResponseCHESTVol. 160Issue 3PreviewWe thank Xiao et al for their commentary on our recent publication.1 They question the linkage between elevated intraabdominal pressure (IAP), which defines intraabdominal hypertension (IAH), and the development of acute kidney injury (AKI). Full-Text PDF The Linkage Between Intraabdominal Hypertension and Acute Kidney Injury Remains To Be ConfirmedCHESTVol. 160Issue 3PreviewWe read with great interest on the study by Dupont et al1 published in CHEST (August 2021), which explored the association between intraabdominal hypertension (IAH) and acute kidney injury (AKI) in patients with COVID-19 who were mechanically ventilated. Although the sample size is small, the study should be commended for providing the first insight into the possible causality between IAH and AKI. However, we would like to stress that causal inference from observational data is challenging and that any linkage identified in this way should be tested in prospective controlled trials. Full-Text PDF