The role of continuous renal replacement therapy in the management of cardiorenal syndrome involving acute myocardial infarction with concomitant pneumonia: case report

¹Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta, Indonesia, ²Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Muhammadiyah Jakarta, Jakarta, Indonesia, ³Department of Anesthesiology and Intensive Care, Universitas Indonesia, Fatmawati Hospital, Jakarta, Indonesia, ⁴Tugu Koja Hospital, Jakarta, Indonesia, ⁵Department of Surgery, Faculty of Medicine, Hasanuddin University, Hasanuddin University Hospital, Makassar, Indonesia

^&Corresponding author
Resiana Karnina, Department of Anesthesiology and Intensive Care, Faculty of Medicine, Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Introduction    

Cardiorenal syndrome (CRS) is a disorder affecting both the heart and kidneys [1]. CRS type 1 manifests in approximately 25% of the patients who are admitted to hospital for acute decompensated heart failure (ADHF). Conservative therapy methods are often inadequate for CRS patients due to ongoing kidney deterioration. Ultrafiltration is an alternative to diuretic therapy for patients with refractory kidney failure, and continuous renal replacement therapy (CRRT) is a potential modality [2,3]. This case report discusses the role of continuous renal replacement therapy (CRRT) in the management of a CRS case with septic shock due to pneumonia.

Patient and observation     

Patient information: a 56-year-old female patient diagnosed with ADHF due to acute myocardial infarction (AMI) had been hospitalized in the intensive cardiac care unit (ICCU) for 16 days. Suddenly, the patient complained of worsening shortness of breath. Revascularization was not performed due to a family disagreement. The patient had a history of stroke infarction one year ago.

Clinical findings: the vital signs of the patient were as follows: GCS E3M4V6, blood pressure 131/68 mmHg, heart rate 71 bpm on dobutamine 5 mcg, respiratory rate 34 breaths/minute. A physical examination revealed rhonchi in both lung fields. During intensive cardiac care, the urine output of the patient decreased and a positive cumulative fluid balance was observed.

Diagnostic assessment: the laboratory tests revealed the following: Hb 9.7 g/dL, leukocytes 16,800/mm³, arterial blood gas analysis indicating respiratory alkalosis (pH 7.56, pCO2 21.9 mmHg, pO2 219.2 mmHg, HCO3 19.8 mEq/L), and procalcitonin 2.93 ng/mL. The echocardiogram showed an ejection fraction (EF) of 33% with a hypokinetic left ventricle. The chest X-ray revealed bilateral infiltrates, left pleural effusion, and cardiomegaly.

Therapeutic interventions: the patient was transferred to the intensive care unit (ICU), intubated, and placed on mechanical ventilation to reduce the breathing effort. Resuscitation with inotropic support and broad-spectrum antibiotics was initiated due to a suspected bacterial infection. A decline in kidney function (urea 228.2 mg/dL, creatinine 3.25 mg/dL, and eGFR 16 mL/min) led to a diagnosis of CRS type 1 with severe septic shock due to pneumonia, and supportive hemodialysis (HD) was performed. On the first day of HD, which lasted 2.5 hours (UF 1000), the hemodynamics of the patient were unstable (blood pressure 126/65 mmHg, heart rate 58 bpm, respiratory rate 32 breaths/minute), and arrhythmia occurred, leading to the discontinuation of HD and the initiation of CRRT.

CRRT was conducted for 48 hours and clinical improvement was observed. Brain perfusion parameters, such as improved consciousness, spontaneous eye-opening, and the ability to follow simple commands (GCS E2M4VETT with endotracheal tube) were accompanied by a blood pressure of 140/84 mmHg, irregular heart rate of 50 bpm, and bigeminy ventricular extrasystole. Kidney function improved with increased urine production (Figure 1), decreased serum creatinine level (to 1.92 mg/dL; Figure 2), and improved eGFR (to 19.36 mL/min; Figure 2). Pneumonia improved with the administration of a combination of antibiotics: meropenem 2g every 8h, levofloxacin 1g per day, and fluconazole 200 mg every 12h. An early tracheostomy was performed considering the longer weaning process from the ventilator in patients with heart failure (HF).

CRRT was discontinued due to filter saturation and supportive hemodialysis was initiated. The acute kidney injury score of the patient improved with a combination of HD and continuous diuretic therapy, achieving fluid balance.

Follow-up and outcome of interventions: on day 7 of treatment, weaning from mechanical ventilation was successful. The patient was transferred to the high-care unit (HCU) on day 10 of treatment, after three days without mechanical ventilation interventions. At this time, the patient showed good consciousness and a urine production of 1.4 mL/kg/h with minimal inotropic support.

Patient perspective: patients showed good consciousness and enough urine production after discharge from ICU.

Informed consent: It was obtained from the patient.

Discussion     

The US National Heart, Lung, and Blood Institute defines CRS as a condition resulting from the close connection between the cardiovascular system and the kidneys that leads to an increase in the amount of circulating blood, an exacerbation of HF, and the onset of kidney disease [4,5]. The initial proposed definition of CRS referred only to the impact of heart damage on pre-existing kidney failure; however, it is currently clear that the heart or kidneys can be the primary location of early injury. Hence, CRS can result from concurrent impairment of both the heart and kidneys, irrespective of the order in which they are affected [4].

According to the Acute Dialysis Quality Initiative (ADQI), CRS can be classified into five subcategories based on disease progression (Table 1). The criteria used to categorize these include the main location of the damage (heart or kidneys), other disorders affecting both organs and the type of condition (acute or chronic). CRS is characterized by heart dysfunction leading to kidney function impairment, whereas cardiorenal syndrome (a subcategory of CRS) is characterized by primary kidney failure that precipitates heart function impairment (Table 2) [4,5].

During acute episodes, CRS type 1 involves a reduction in cardiac function that results in renal function impairment. Renal impairment is present in 25% of patients diagnosed with ADHF. The incidence of CRS type 1 is 25.4%, with more than 30% of patients hospitalized for ADHF having a history of kidney insufficiency and 20% presenting with serum creatinine levels greater than 2.0 mg/dL [4].

The patient in this case study had ADHF and an increase in serum creatinine level (3.25 mg/dL). The decline of kidney function was linked to renal hypoperfusion resulting from reduced cardiac output. ADHF resulted in both elevated central venous pressure (CVP) and volume overload. The congestion and elevated venous pressure diminished the blood flow rate within the glomerular capillary system, leading to sluggish intravascular flow, glomerular dysfunction, and reduced urine output. Increased CVP has also been directly linked to kidney function (Figure 3) [4].

The renin-angiotensin-aldosterone system (RAAS) contributes to the progression of kidney damage and the exacerbation of HF. In HF patients, this neurohormonal pathway is implicated in the restoration of tissue perfusion. Elevated renin levels can affect a rise in angiotensin II (Ang II), which can cause systemic detrimental impacts on the kidneys. Ang II induces efferent arteriolar vasoconstriction and increased renal plasma flow filtered via the glomerulus, leading to reduced hydrostatic pressure, enhanced elevated peritubular oncotic pressure, and salt reabsorption in the proximal tubule. Ang II also stimulates the synthesis of endothelin-1 (ET-1) in the kidneys and improves the aldosterone-stimulated reabsorption of sodium in the distal nephron. The peptide ET-1 is a profibrotic and proinflammatory agent, as well as a powerful vasoconstrictor that induces renal injury through pathological alterations. Moreover, the increase in oxidative stress involves activation of the sympathetic nervous system, stimulation of the RAAS, and volume expansion. In addition, nephrotoxic drugs such as certain antibiotics and nonsteroidal anti-inflammatory drugs administered to ADHF patients during inpatient hospital treatment can decrease kidney function [4].

The escalation of kidney failure can be attributed to its manifestation and possible etiology, as well as its correlation with diuretic response and functional condition. Complete decongestion should be achieved in patients who have positive diuretic responses, as residual congestion at hospital discharge is the primary predictor of readmission [2,6]. It is essential to ensure the optimal dosage is administered, provide a first evaluation of the diuretic effect by measuring urine volume and sodium excretion, and promptly increase the diuretic dosage when needed. The European Society of Cardiology HF guidelines (2021) recommend that vasodilators be used with ADHF patients (with systolic blood pressures more than 90 mmHg) who are hemodynamically stable. Patients with fluid overload and progressive acute kidney injury should generally be provided ultrafiltration as a final option [3]; however, early ultrafiltration may improve prognosis [2].

Hemodialysis (HD) is the removal of solutes through diffusion across a membrane from a region of high concentration to one of low concentration. During dialysis, a semi-permeable membrane separates the flow of blood from that of the dialysate, which is an electrolyte solution, and the two flow in opposite directions. Hemofiltration involves the pressure differential between the two sides of the dialysis membrane inducing the convection of water (ultrafiltration) and the release of tiny to medium-sized molecules. These molecules then flow through the more permeable membrane and are considered waste [7]. Dialysis is typically required when pharmaceutical therapies are no longer effective in controlling the hypervolemia or systemic toxification induced by renal excretion malfunction. However, in the context of CRS, dialysis is defined in a more comprehensive manner (conventional hemodialysis, peritoneal dialysis, extracorporeal ultrafiltration, continuous procedures) and may be utilized in cases with only moderate impairments. The primary condition for the use of dialysis is refractory hypervolemia (since diuretics are generally ineffective for this condition) [6].

In the case patient, HD was performed on day 2 of ICU treatment; however, the patient experienced arrhythmia during the dialysis process and HD was discontinued and replaced with CRRT. After 48 hours of CRRT, consciousness and kidney function improved, while creatinine level and urine production decreased. Increased mortality rates are directly proportional to the decline in urine output per hour or the rise in serum creatinine level [2]. Promptly implementing hemofiltration, effectively managing infective inflammation and fluid overload, and maintaining a stable cardiac and renal hemodynamic cycle can improve the prognosis [8].

Common indicators to favor the use of CRRT procedures include: 1) biochemical markers, such as urea and creatinine, which have different threshold values (many studies have confirmed that early or preventative use of CRRT significantly improves survival when compared to delayed CRRT treatment); 2) oliguria onset (one study revealed that initiating dialysis when the urine volume declined to below 30 mL/h resulted in a superior survival rate compared to initiation at volumes below 20 mL/h); 3) fluid volume status (one study indicated that a positive fluid balance was significantly linked to high mortality rates) [8].

CRRT plays a role in cytokine removal. Elevated levels of circulating cytokines (IL-6, and TNFα) are present in chronic HF cases, particularly those caused by cardiomyopathy, and these inflammatory signaling mediators can lead to dilation and hypertrophy and contribute to poor prognosis and the advancement of left ventricular dysfunction. Continuous veno-venous hemofiltration (CVVH) can enhance the survival of patients with cardiomyopathy, possibly due to the non-specific elimination of extracorporeal cytokines, resulting in longer duration of each treatment and smaller ultrafiltration rates [2]. In addition, ultrafiltration removes a greater amount of sodium than diuretic therapy using the same amount of water and produces more accurate fluid target determinations [7].

Conclusion     

Patients with ADHF treated in the hospital may develop CRS, which can increase mortality. The use of CRRT can be a therapeutic option for patients with CRS. Through ultrafiltration, CRRT is capable of removing circulating cytokines in the blood, reducing volume overload, and addressing electrolyte imbalance, thereby enhancing the function of the heart and kidneys and potentially improving prognoses.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Data curation: Resiana Karnina, Vera Irawany and Sidharta Kusuma Manggala; Resources: Resiana Karnina, Vera Irawany, Sidharta Kusuma Manggala, and Muhammad Faruk; Writing original draft: Resiana Karnina, Vera Irawany, Sidharta Kusuma Manggala, Justika Usmadhani Aulya, and Muhammad Faruk. Reviewing and editing: Sidharta Kusuma Manggala, Justika Usmadhani Aulya, and Muhammad Faruk. All the authors read and approved the final version of this manuscript.

Tables and figures     

Table 1: five cardiorenal syndrome (CRS) subtypes (adapted from Rangaswami et al. [5])

Table 2: pathophysiology of CRS (adapted from Prastaro et al.[4] )

Figure 1: urine output, diuresis, and balance development of the case patient during ICU admission

Figure 2: changes in BUN, e-GFR, creatinine, and blood lactate levels of the patient during ICU admission

Figure 3: pathophysiology of CRS-Type 1 [4]

References