Our study was a 3-year prospective, open-labeled, randomized, controlled study conducted at a single critical care unit (CCU) in a tertiary care hospital. This study was performed in accordance with the Egyptian National Commission for Bioethics (National Commission for UNESCO) statement on ethical conduct in human research, study procedures were carried out following the Code of Ethics of the World Medical Association (Declaration of Helsinki), study design and protocol were reviewed and approved by the human ethics committee of Cairo university, study was registered and issued a trial registration number (I-111015), study participants signed written informed consents, study data was anonymized, and the privacy rights of the study participants were observed diligently.
Study participants were CKD and CCS patients, candidate for diagnostic coronary angiography or PCI, and referred to the CCU. The study participants were subjected to history taking and data collection for age, gender, hypertension, DM, dyslipidemia, smoking, cerebrovascular disease, PVD, acute coronary syndrome (ACS), prior coronary angiography, and prior revascularization procedure. In addition, study participants were subjected to comprehensive clinical examination including measurement of vital signs on admission (systolic and diastolic blood pressure, heart rate, respiratory rate, and body temperature), mean arterial blood pressure, body weight and height, admission and discharge twelve-lead electrocardiograms (ECGs), transthoracic echocardiography (TTE), complete blood count, fasting blood glucose, blood urea, serum creatinine, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, creatinine kinase (CK), creatine kinase-MB (CK-MB), and troponin. Normal values for ECG waves and intervals were referenced to the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Electrocardiography) report . Data documented with ECGs included arrhythmias, new bundle branch block, ST segment elevation, ST segment depression, changes of T wave, or no significant changes. Data documented with TTE included left ventricular ejection fraction (LVEF). The preprocedural CKD was categorized based on the estimated glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) formula into mild CKD (60-89 ml/min/1.73 m2), moderate CKD (30-59 ml/min/1.73 m2), and severe CKD (15-29 ml/min/1.73 m2), respectively . Screened participants were enrolled if they had CKD, CCS after previous episode of ACS including ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), or unstable angina (UA), and planned for diagnostic coronary angiography or PCI. Screened participants with normal kidney functions, single functioning kidney, end stage renal disease (ESRD) on regular dialysis, history of kidney transplant, AKI triggered by cocaine, surgery, sepsis, trauma, or cardiogenic shock, pulmonary edema, acute heart failure with LVEF <30%, systolic blood pressure <80 mmHg, bronchial asthma, multiple myeloma, pregnancy, allergy to phentolamine or CM, or received barbiturates, antipsychotic agents, phosphodiestrase-5 inhibitors, CM within 7 days of study entry, or α-adrenoreceptor blocker at the time of admission were excluded from the study.
One hundred and seven eligible participants were randomly, consecutively assigned with an equal 1:1 allocation ratio into an open-labeled unblinded fashion. The enrolled study participants were randomized into 2 groups of 52 participants for conventional CIN-AKI prevention strategy with normal saline infusion at a rate of 1-1.5 ml/kg/hr to be started 12 hours before coronary angiography or PCI and continued for 24 hours after CM exposure in addition to 2 doses of N-acetylcysteine 600-1200 mg per oral the day before admission and 2 doses on the day of the procedure (Group 1) versus 55 age and gender matched participants for phentolamine 1-5 mg intravenous (IV) bolus followed by continuous IV infusion at a rate of 0.5-20 μgm/kg/min to be started 1 hour before coronary angiography or PCI and continued for 4-6 hours after CM exposure in addition to β-adrenoceptor blocker and conventional CIN-AKI prevention strategy (Group 2).
The study evaluated the incidence of CIN-AKI, association of periprocedural phentolamine with prevention of CIN-AKI, change in urine output, serum creatinine and eGFR, and incidence of major adverse cardiac and cerebrovascular events (MACCE) in CKD patients undergoing coronary catheterization.
The assessment outcomes were coded, and the data was analyzed with the Statistical Package for the Social Sciences software (SPSSÒ) version 25. Quantitative (continuous) data was expressed as means and standard deviations, while qualitative (categorial) data was expressed as frequencies and percentages. Comparisons between parametrically distributed quantitative variables were done with the Independent two-tailed t-test, between non-parametrically distributed quantitative variables with Mann-Whitney test, and between qualitative variables with Chi-square test, respectively [9,10]. The confidence interval was set to 95% and the margin of error accepted was set to 5%. Any comparison considered statistically significant was at P < 0.05 or less and highly significant at P < 0.01.