lisinopril and Multiple-Organ-Failure

The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ~24 mg m d started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg d from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.

Topics: Acute Disease; Acute Radiation Syndrome; Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluid Therapy; Lisinopril; Multiple Organ Failure; Radiation Dosage; Radiation-Protective Agents; Rats; Survival Rate; Treatment Outcome; Water

Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome.. Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Atenolol; Cardiovascular Agents; Chlorthalidone; Combined Modality Therapy; Decontamination; Drug Overdose; Emergency Service, Hospital; Endoscopy, Digestive System; Extracorporeal Membrane Oxygenation; Female; Humans; Lisinopril; Multiple Organ Failure; Renal Dialysis; Shock, Cardiogenic; Tablets; Transcutaneous Electric Nerve Stimulation; Treatment Outcome

In general, angiotensin converting enzyme (ACE) inhibitors should be discontinued in pregnancy, as they can induce an ACE fetopathy. For the treatment of the latter, early peritoneal dialysis is recommended for in utero exposure to captopril and enalapril, although the outcome is poor. Early peritoneal dialysis has not previously been reported for lisinopril induced multiorgan failure. A case is reported in which treatment was given on postnatal day 3. The patient recovered from oligoanuria to almost normal renal function, and heart, brain, and musculoskeletal injury was reversible. This is despite relatively poor clearance of the drug through peritoneal dialysis. Analysis of the pharmacokinetic data suggests that haemodialysis or haemofiltration would be more efficacious for removal of the drug, and these treatments should be performed if available.

Topics: Angiotensin-Converting Enzyme Inhibitors; Female; Humans; Hypertension; Infant, Newborn; Lisinopril; Maternal-Fetal Exchange; Multiple Organ Failure; Peritoneal Dialysis; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects

To determine the effect of preoperative therapy with angiotensin-converting enzyme (ACE) inhibitors on clinical outcome after cardiovascular surgery.. Inception cohort.. A tertiary care 54-bed cardiothoracic ICU.. All admissions to an ICU over a 42-month period after cardiovascular surgery.. Extraction of preoperative, operative, and ICU data from a database.. Incidence of acute organ dysfunction, length of mechanical ventilation, ICU stay, and death after cardiovascular surgery.. The study cohort consisted of four groups: normal or moderately impaired left ventricular function control (group A, n=6,400); normal or moderately impaired left ventricular function treated with ACE inhibitors (group B, n=1,375); severe left ventricular dysfunction control (group C, n=1,905); and severe left ventricular dysfunction treated with ACE inhibitors (group D, n=1,650). The incidence of three or more organ dysfunction was similar on comparison of group A vs group B (5% vs 6%) or group C vs group D (15% vs 13%). There were no differences in the total duration of mechanical ventilation or length of stay in the ICU in group A vs group B or group C vs group D. Death occurred in 2% of groups A and B, and at 6% in groups C and D. Preoperative severe left ventricular dysfunction in both groups C and D was associated with an increased incidence of three or more organ dysfunction, duration of mechanical ventilation, length of stay in ICU, and death after surgery. Multivariate analysis indicated that therapy with ACE inhibitors did not affect the clinical outcome after cardiovascular surgery.. Preoperative therapy with ACE inhibitors did not influence the clinical outcome after cardiac surgery. It is unlikely that therapy with ACE inhibitors can alter the clinical sequelae of cardiopulmonary bypass and cardiac surgical procedures performed in high-risk patients because of underlying severe left ventricular dysfunction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiopulmonary Bypass; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Case-Control Studies; Electrocardiography; Enalapril; Female; Follow-Up Studies; Hospital Mortality; Humans; Incidence; Intra-Aortic Balloon Pumping; Lisinopril; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Preoperative Care; Retrospective Studies; Treatment Outcome; Ventricular Dysfunction, Left