Cooling to Prevent Radiocontrast Nephropathy - COOL-RCN

Jun 27, 2011
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Radiant Medical, subsequently assumed by Zoll Circulation
Date Presented:
01/01/2008
Date Published:
01/01/2011
Date Updated:
06/27/2011
Original Posted Date:
06/27/2011
References

Description:

Contrast-induced nephropathy (CIN) post-cardiac catheterization has been associated with poor outcomes. Patients with pre-existing renal dysfunction are at especially higher risk of developing CIN. The current trial sought to determine the utility of systemic hypothermia in patients with a creatinine clearance between 20 and 50 ml/min receiving iodinated contrast.

Hypothesis:

Systemic hypothermia to 33°C to 34°C would be associated with a decreased incidence of CIN compared with routine management.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 136
Mean Follow Up: 30 days
Mean Patient Age: 73 years
Female: 40%

Patient Populations:

Creatinine clearance between 20 and 50 ml/min undergoing diagnostic and/or interventional catheterization with expected dye load >50 cc

Exclusions:

  • Unstable renal function, acute renal failure, or dialysis
  • Renal artery angiography, renal drug infusion, or known renal artery stenosis
  • Receiving mannitol or IV diuretics
  • Decompensated heart failure, intubated, or hypotension
  • ST-elevation MI within 72 hours
  • Severe allergy (contrast, heparin, meperidine, buspirone) or recent monoamine oxidase inhibitor use
  • Additional contrast within 10 days pre- or post-procedure
  • Inferior vena cava filter, or height <4’ 11" 
  • Hypersensitivity to hypothermia (Raynaud’s), bleeding diathesis, coagulopathy, sickle cell disease, severe hepatic impairment, cryoglobulinemia, untreated hypothyroidism, Addison’s, BPH or urethral stricture, or refusal for blood transfusions

Primary Endpoints:

  • Incidence of CIN, defined as a relative increase in serum creatinine >25% from baseline to any time within 96 hours
  • Incidence of 30-day adverse events, including death, myocardial infarction (MI), ventricular fibrillation, venous complications requiring surgery, bleeding, or rehospitalization

Drug/Procedures Used:

Systemic hypothermia, with a target core temperature of 33°C, was initiated before contrast administration, and maintained until 3 hours after the procedure. Rewarming was initiated after 3 hours with a target of 36°C at a rate of 1°C/hr. In addition, all patients received intravenous (IV) hydration with normal saline (1.5 cc/kg/hr) or one-half normal saline for patients with congestive heart failure or left ventricular dysfunction at 1.0 cc/kg/hr for 2-12 hours precatheterization. One hour prior to cath, normal saline was stopped, and a bicarbonate drip at 3 ml/kg/hr was initiated for 1 hour, followed by 1 ml/kg/hr for 5-7 hours post-procedure.

Concomitant Medications:

Shivering suppressing protocol, consisting of buspirone, meperidine, and surface forced air warming blanket, was utilized 45-60 minutes prior to the procedure in the systemic hypothermia group.

Principal Findings:

A total of 136 patients were randomized, 63 to systemic hypothermia, and 73 to routine management (normothermia). The trial was terminated at this point due to financial insolvency of the sponsor, Radiant Medical. Baseline characteristics were fairly similar between the two groups, except diabetes, which was more frequent in the normothermia group. N-acetylcysteine was used in about 70% of the patients. The pre- and post-hydration volumes in both arms were about 900 ml. The total amount of contrast used during the procedure was about 142 cc. Non-ionic low osmolar contrast was used in about 24% of the patients.

The mean time to achieve a core temperature of 33°C was about 29.4 minutes; a temperature of 34°C was achieved in about 92.5% of the patients. Baseline serum creatinine was similar between the two arms (mean around 1.9 mg/dl), with a creatinine clearance of about 36-37 ml/min.

There was no difference in the incidence of CIN between the hypothermic and normothermic patients (22.4% vs. 18.6%, odds ratio 1.27, 95% confidence interval 0.53-3.00, p = 0.59). There was also no difference in serum creatinine between the two arms at 24 hours (p = 0.3), 48 hours (p = 0.09), or 72-96 hours (p = 0.18). Overall 30-day MACE rates were similar between the two arms (37.9% vs. 37.1%, p = 0.93). All-cause mortality at 30 days tended to be higher in the hypothermia group compared with the normothermia group, although this was not statistically significant (5.2% vs. 1.4%, p = 0.33). Bradycardia requiring treatment (12.1% vs. 2.9%, p = 0.04), and nausea or vomiting (44.8% vs. 8.6%, p < 0.0001) were significantly higher in the hypothermia group. All other 30-day adverse events, including the need for dialysis, were similar between the two groups.

Interpretation:

The results of this trial indicate that systemic hypothermia is not superior to routine hydration in patients with renal dysfunction undergoing cardiac catheterization, despite being more invasive and technically difficult. One significant limitation is that although the COOL-RCN trial aimed for, and was powered for, 400 patients, only 136 patients could be enrolled.

References:

Stone GW, Vora K, Schindler J, et al., on behalf of the COOL-RCN Investigators. Systemic Hypothermia to Prevent Radiocontrast Nephropathy (From the COOL-RCN Randomized Trial). Am J Cardiol 2011;Jun 13:[Epub ahead of print].

Presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2008), Washington, DC, October 2008.

Keywords: Nausea, Vomiting, Cardiac Catheterization, Coronary Disease, Creatinine, Renal Dialysis, Temperature, Kidney Diseases, Bicarbonates, Rewarming, Hypothermia, Heart Failure, Bradycardia, Ventricular Dysfunction, Left, Diabetes Mellitus


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