Cardio-Pulmonary-Renal Consequences of Severe COVID-19

Severe acute respiratory syndrome coronavirus 2 has rapidly spread worldwide and resulted in the coronavirus disease 2019 (COVID-19) pandemic. The disease raised an unprecedented demand for intensive care support due to severe pulmonary dysfunction and multiorgan failure. Although the pulmonary system is the potential target of the COVID-19, recent reports have demonstrated that COVID-19 profoundly influences the cardiovascular system and the kidneys. Research studies on cadavers have shown that direct heart and kidney injury can be frequently seen in patients deceased due to COVID-19 infection. On the other hand, functional or structural dysfunction of the heart may deteriorate the renal function and vice versa. This concept is already known as the cardiorenal syndrome and may play a role in COVID-19. Proactive monitoring of micro- and macrohemodynamics could allow prompt correction of circulatory dysfunction and can be of pivotal importance in the prevention of acute kidney injury. Moreover, type and amount of fluid therapy and vasoactive drug support could help manage these patients either with or without mechanical ventilator support. This brief review outlines the current evidence regarding the COVID-19-related renal and cardiorenal complications and discusses potential hemodynamic management strategies.

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Cardiogenic shock and acute kidney injury: the rule rather than the exception

Heart Failure Reviews ◽

10.1007/s10741-020-10034-0 ◽

2020 ◽

Author(s):

N Ghionzoli ◽

C Sciaccaluga ◽

GE Mandoli ◽

G Vergaro ◽

F Gentile ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiogenic Shock ◽

Severe Depression ◽

Kidney Injury ◽

Cardiorenal Syndrome ◽

Current Evidence ◽

Evidence Based ◽

Threatening Condition ◽

Life Threatening ◽

Worse Prognosis

Abstract Cardiogenic shock (CS) is a life-threatening condition of poor end-organ perfusion, caused by any cardiovascular disease resulting in a severe depression of cardiac output. Despite recent advances in replacement therapies, the outcome of CS is still poor, and its management depends more on empirical decisions rather than on evidence-based strategies. By its side, acute kidney injury (AKI) is a frequent complication of CS, resulting in the onset of a cardiorenal syndrome. The combination of CS with AKI depicts a worse clinical scenario and holds a worse prognosis. Many factors can lead to acute renal impairment in the setting of CS, either for natural disease progression or for iatrogenic causes. This review aims at collecting the current evidence-based acknowledgments in epidemiology, pathophysiology, clinical features, diagnosis, and management of CS with AKI. We also attempted to highlight the major gaps in evidence as well as to point out possible strategies to improve the outcome.

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Combined Renal-Pulmonary Extracorporeal Support with Low Blood Flow Techniques: A Retrospective Observational Study (CICERO Study)

Blood Purification ◽

10.1159/000517280 ◽

2021 ◽

pp. 1-10

Author(s):

Guglielmo Consales ◽

Lucia Zamidei ◽

Franco Turani ◽

Diego Atzeni ◽

Paolo Isoni ◽

...

Keyword(s):

Mechanical Ventilation ◽

Observational Study ◽

Multiorgan Failure ◽

Invasive Mechanical Ventilation ◽

Respiratory Acidosis ◽

Kidney Injury ◽

Protective Ventilation ◽

Retrospective Observational Study ◽

Organ Support ◽

Chronic Obstructive

Background: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (<400 mL/min). Objectives: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit. Methods: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded. Results: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded. Conclusion: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI.

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Trauma-Induced Coagulopathy: Overview of an Emerging Medical Problem from Pathophysiology to Outcomes

Medicines ◽

10.3390/medicines8040016 ◽

2021 ◽

Vol 8 (4) ◽

pp. 16

Author(s):

Gabriele Savioli ◽

Iride Francesca Ceresa ◽

Luca Caneva ◽

Sebastiano Gerosa ◽

Giovanni Ricevuti

Keyword(s):

Major Trauma ◽

Management Strategies ◽

Medical Problem ◽

Current Evidence ◽

Potential Drug ◽

The Past ◽

Trauma Induced Coagulopathy ◽

Threatening Condition ◽

Life Threatening ◽

Trauma Mortality

Coagulopathy induced by major trauma is common, affecting approximately one-third of patients after trauma. It develops independently of iatrogenic, hypothermic, and dilutive causes (such as iatrogenic cause in case of fluid administration), which instead have a pejorative aspect on coagulopathy. Notwithstanding the continuous research conducted over the past decade on Trauma-Induced Coagulopathy (TIC), it remains a life-threatening condition with a significant impact on trauma mortality. We reviewed the current evidence regarding TIC diagnosis and pathophysiological mechanisms and summarized the different iterations of optimal TIC management strategies among which product resuscitation, potential drug administrations, and hemostatis-focused approaches. We have identified areas of ongoing investigation and controversy in TIC management.

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Renal Manifestations of Covid-19: Physiology and Pathophysiology

Journal of Clinical Medicine ◽

10.3390/jcm10061216 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1216

Author(s):

Zaher Armaly ◽

Safa Kinaneh ◽

Karl Skorecki

Keyword(s):

Viral Replication ◽

Virus Disease ◽

Multiorgan Failure ◽

Critical Role ◽

Kidney Injury ◽

Small Sample ◽

Renal Physiology ◽

High Morbidity ◽

Enzymatic Production ◽

High Incidence

Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated. Kidney susceptibility to SARS-CoV-2 infection is determined by the presence of angiotensin-converting enzyme 2 (ACE2) receptor which is used as port of the viral entry into targeted cells, tissue tropism, pathogenicity and subsequent viral replication. The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7), which exerts vasodilatory, anti-inflammatory, antifibrotic and diuretic/natriuretic actions via activation of the Mas receptor axis. Loss of this activity constitutes the potential basis for the renal damage that occurs in COVID-19 patients. Indeed, several studies in a small sample of COVID-19 patients revealed relatively high incidence of acute kidney injury (AKI) among them. Although SARS-CoV-1 -induced AKI was attributed to multiorgan failure and cytokine release syndrome, as the virus was not detectable in the renal tissue of infected patients, SARS-CoV-2 antigens were detected in kidney tubules, suggesting that SARS-CoV-2 infects the human kidney directly, and eventually induces AKI characterized with high morbidity and mortality. The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role. The current review focuses on the critical role of ACE2 in renal physiology, its involvement in the development of kidney injury during SARS-CoV-2 infection, renal manifestations and therapeutic options. The latter includes exogenous administration of Ang (1-7) as an appealing option, given the high incidence of AKI in this ACE2-depleted disorder, and the benefits of ACE2/Ang1-7 including vasodilation, diuresis, natriuresis, attenuation of inflammation, oxidative stress, cell proliferation, apoptosis and coagulation.

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Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations

Nutrients ◽

10.3390/nu13051601 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1601

Author(s):

Jennifer Wilbrink ◽

Gwen Masclee ◽

Tim Klaassen ◽

Mark van Avesaat ◽

Daniel Keszthelyi ◽

...

Keyword(s):

Energy Intake ◽

Oral Delivery ◽

Regional Differences ◽

Management Strategies ◽

Inhibitory Effect ◽

Current Evidence ◽

Ileal Brake ◽

Regional Effects ◽

Clinical Observations ◽

Intestinal Delivery

Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.

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Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond

Journal of Clinical Medicine ◽

10.3390/jcm10061175 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1175

Author(s):

Emaad M. Abdel-Rahman ◽

Faruk Turgut ◽

Jitendra K. Gautam ◽

Samir C. Gautam

Keyword(s):

Acute Kidney Injury ◽

Kidney Disease ◽

Kidney Injury ◽

Complete Recovery ◽

Severe Form ◽

Clinical Syndrome ◽

Current Evidence ◽

Clinical Predictors ◽

End Stage

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

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Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial

BMC Anesthesiology ◽

10.1186/s12871-021-01288-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qiong-Fang Wu ◽

Hao Kong ◽

Zhen-Zhen Xu ◽

Huai-Jin Li ◽

Dong-Liang Mu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Partial Nephrectomy ◽

Controlled Trial ◽

Intervention Group ◽

Kidney Injury ◽

Control Group ◽

Hemodynamic Management ◽

Randomized Controlled ◽

Renal Hilum ◽

Pilot Randomized Controlled Trial

Abstract Background The incidence of acute kidney injury (AKI) remains high after partial nephrectomy. Ischemia-reperfusion injury produced by renal hilum clamping during surgery might have contributed to the development of AKI. In this study we tested the hypothesis that goal-directed fluid and blood pressure management may reduce AKI in patients following partial nephrectomy. Methods This was a pilot randomized controlled trial. Adult patients who were scheduled to undergo partial nephrectomy were randomized into two groups. In the intervention group, goal-directed hemodynamic management was performed from renal hilum clamping until end of surgery; the target was to maintain stroke volume variation < 6%, cardiac index 3.0–4.0 L/min/m2 and mean arterial pressure > 95 mmHg with crystalloid fluids and infusion of dobutamine and/or norepinephrine. In the control group, hemodynamic management was performed according to routine practice. The primary outcome was the incidence of AKI within the first 3 postoperative days. Results From June 2016 to January 2017, 144 patients were enrolled and randomized (intervention group, n = 72; control group, n = 72). AKI developed in 12.5% of patients in the intervention group and in 20.8% of patients in the control group; the relative reduction of AKI was 39.9% in the intervention group but the difference was not statistically significant (relative risk 0.60, 95% confidence interval [CI] 0.28–1.28; P = 0.180). No significant differences were found regarding AKI classification, change of estimated glomerular filtration rate over time, incidence of postoperative 30-day complications, postoperative length of hospital stay, as well as 30-day and 6-month mortality between the two groups. Conclusion For patients undergoing partial nephrectomy, goal-directed circulatory management during surgery reduced postoperative AKI by about 40%, although not significantly so. The trial was underpowered. Large sample size randomized trials are needed to confirm our results. Trial registration Clinicaltrials.gov identifier: NCT02803372. Date of registration: June 6, 2016.

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SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2233 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Pouneh Pasha ◽

Graydon S Meneilly ◽

Jordanna Esther Kapeluto

Keyword(s):

Surgical Resection ◽

Myocardial Infarct ◽

Kidney Injury ◽

Volume Overload ◽

Cardiorenal Syndrome ◽

Intermittent Hemodialysis ◽

Close Monitoring ◽

Clinical Pharmacokinetics ◽

Reduced Ejection Fraction ◽

Supportive Management

Abstract Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N&lt95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.

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Severe Decompression Illness: Case Report, Prehospital Recognition, and Regional Transport Considerations

Case Reports in Emergency Medicine ◽

10.1155/2017/7203085 ◽

2017 ◽

Vol 2017 ◽

pp. 1-4

Author(s):

Julie Estrada ◽

David Meurer ◽

Kevin De Boer ◽

Karl Huesgen

Keyword(s):

Early Recognition ◽

Multiorgan Failure ◽

Tertiary Care ◽

Pulmonary Arteries ◽

Kidney Injury ◽

Decompression Illness ◽

Arterial Blood Gas ◽

Head Ct ◽

Arterial Blood ◽

Prehospital Emergency

A 46-year-old male presented to our tertiary care emergency department (ED) with shortness of breath and chest pain following an uneventful four-hour SCUBA dive at 100 feet. His prehospital emergency medical services (EMS) assessment revealed transient hypotension and hypoxia. He later developed progressive skin mottling. Serology was significant for acute kidney injury, transaminitis, hemoconcentration, and hypoxia on an arterial blood gas. Computed tomography (CT) angiography demonstrated intravascular gas throughout the mesenteric and pulmonary arteries as well as the portal venous system. No abnormality was seen on head CT and the patient had normal mental status. Prehospital nonrebreather oxygen therapy was changed to continuous positive airway pressure (CPAP) upon ED arrival, and the patient was intubated prior to transfer to a hyperbaric facility. However, within 24 hours the patient was found to have multiorgan failure, diffuse cerebral edema, and brain death despite no further episodes of hypotension or hypoxia. No intracranial gas was seen on repeat head CT. Our case demonstrates the importance of early recognition of decompression illness by EMS personnel, consideration of ground versus flight transportation of these patients to the nearest hyperbaric center, and the possible use of prehospital CPAP as an alternative to enhance oxygenation.

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Toward the diagnosis of rare childhood genetic diseases: what do parents value most?

European Journal of Human Genetics ◽

10.1038/s41431-021-00882-1 ◽

2021 ◽

Author(s):

Samantha Pollard ◽

Deirdre Weymann ◽

Jessica Dunne ◽

Fatemeh Mayanloo ◽

John Buckell ◽

...

Keyword(s):

Focus Groups ◽

Genetic Disease ◽

Diagnostic Yield ◽

Management Strategies ◽

Health Benefit ◽

Sampling Technique ◽

Evidence Base ◽

Current Evidence ◽

Genomic Testing ◽

Current Evidence Base

AbstractGenomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. We examine whether the current evidence base reflects public tolerance for uncertainty for genomics to diagnose rare childhood genetic disease. We conducted focus groups with general population parents in Vancouver, Canada, and Oxford, United Kingdom, to discuss expectations and concerns related to genomic testing to diagnose rare childhood genetic disease. Applying a purposive sampling technique, recruitment continued until thematic saturation was reached. Transcripts were analysed using thematic analysis. Thirty-three parents participated across four focus groups. Participants valued causal diagnoses alongside management strategies to improve patient health and wellbeing. Further, participants valued expanding the evidence base to reduce evidentiary uncertainty while ensuring security of information. Willingness to pay out of pocket for testing reflected perceived familial health benefit. Diagnostic yield fails to fully capture valued outcomes, and efforts to resolve uncertainty better reflect public priorities. Evaluations of genomic testing that fully integrate valued endpoints are necessary to ensure consistency with best practices and public willingness to accept the uncertain familial benefit.

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