Induced hypothermia by central venous infusion: Saline ice ...

1 Induced hypothermia by central venous infusion : Saline ice slurryversus chilled salineTerry L. Vanden Hoek, MD; Kenneth E. Kasza, PhD; David G. Beiser, MD, MS;Benjamin S. Abella, MD, MPhil; Jeffery E. Franklin, AAS; John J. Oras, PhD; Jason P. Alvarado, BA;Travis Anderson, BS; Hyunjin Son, BS; Craig L. Wardrip, DVM; Danhong Zhao, MD, PhD;Huashan Wang, MD, MS; Lance B. Becker, MDCardiac arrest survivors oftenhave severe neurologic se-quelae that contribute to theirearly mortality and poor func-tional recovery. Induced postresuscitativehypothermia was first reported almost 40yrs ago as a technique for improvingfunctional outcomes after cardiac arrest(1, 2). The conceptual appeal of suchtherapeutic hypothermia stemmed pri-marily from the notion that decreases incore temperature lead to decreased cellu-lar metabolic demand.

2 Cerebral meta-bolic demand decreases by approximately6% per degree Celsius (3). Despite this,postresuscitative hypothermia waslargely abandoned as a difficult and re-source-intensive technique with uncer-tain clinical , the clinical induction of hy-pothermia has found widespread accep-tance in the perioperative setting duringcardiac bypass and certain neurosurgicalprocedures. In the surgical setting, un-like cardiac arrest, hypothermia is in-duced before the ischemic insult , in the relatively controlled envi-ronment of the operating suite, hypo-thermia induction has been a viable ther-apeutic option that is protective againstconditions of altered blood flow. In addi-tion, hypothermia has also been appliedto the treatment of malignant hyperther-mia, traumatic brain injury, and acutemyocardial infarction (4 7).

3 Two recent multiple-center, prospec-tive studies of comatose survivors of out-of-hospital cardiac arrest demonstratedimproved neurologic outcome at hospitaldischarge (8) and improved neurologicoutcome and mortality rate at 6 months(9) in patients receiving 12 24 hrs ofhypothermia (32 34 C) after return ofspontaneous circulation. Based on thestrength of these findings, the Interna-tional Liaison Committee on Resuscita-tion recommended the induction of ther-apeutic hypothermia for 12 24 hrs inselected comatose survivors after out-of-hospital cardiac arrest with initial ven-tricular fibrillation (10). The InternationalLiaison Committee on Resuscitation advi-sory statement calls for the developmentof hypothermia -induction techniquesFrom the University of Chicago, Section of Emer-gency Medicine, Chicago, IL (TLVH, DGB, BSA, JA, TA,LBB); Argonne National Laboratory, Energy TechnologyDivision, Argonne, IL (KEK, JEF, JJO, HS); and theUniversity of Chicago, Animal Resource Center, Chi-cago, IL (CLW).

4 Supported, in part, by NIH/NHLBI through 1RO1(HL67630) and through a grant from the Laerdal Vanden Hoek and Ken Kasza share firstauthorship of this article on the basis of their majorcontributions in working with Dr. Becker in the con-ception, planning, and execution of the experiments;David Beiser is second author for taking primary re-sponsibility for writing the manuscript, analyzing data,and modeling the heat 2004 by the Society of Critical CareMedicine and Lippincott Williams & WilkinsDOI: :Surface cooling improves outcome in selected co-matose survivors of cardiac arrest. Internal cooling with consid-erable volumes of intravenous cold Saline may accelerate hypo-thermia induction. This study compares core temperatures inswine after central catheter infusions of Saline ice slurry (salinewith smoothed 100- m-size ice particles) vs.

5 An equal volume ofchilled Saline . We hypothesized that slurry would achieve corehypothermia (32 34 C) more consistently and at a faster :A total of 11 swine were randomized to receive mi-croparticulate ice slurry, chilled Saline infusion , or anesthesiaalone in a monitored laboratory :Intravenous bolus (50 mL/kg) of slurry or NaCl Saline . Slurry was composed of a 1:1 mixture of ice anddistilled H2O plus :Cerebral cortex, tympanic membrane, inferiorvena cava, rectal temperatures, electrocardiogram, arterial bloodpressure, and arterial oxygen saturation were recorded for 1 hrafter Results:Compared with anesthetized controls, core braintemperatures of the Saline and slurry groups dropped by C and C (p.)

6 009), respectively. With an infusionrate of 120 mL/min, cooling rates for the Saline and slurry groupswere C/hr and C/hr, respectively,during the first 20 mins. Four of four animals in the slurry groupvs. zero of four animals in the Saline group achieved targetcortical temperatures of<34 :Cold intravenous fluids rapidly induce hypothermia inswine with intact circulation. A two-phase (liquid plus ice) Saline slurrycools more rapidly than an equal volume of cold Saline at 0 C. Ice-slurrycould be a significant improvement over other cooling methods whenrate of cooling and limited infusion volumes are important to the clini-cian. (Crit Care Med 2004; 32[Suppl.]:S425 S431)KEYWORDS: Induced hypothermia ; therapeutic hypothermia ;cooling; resuscitation; cardiac arrest; swine; slurry; intravenous; Saline ; core temperatureS425 Crit Care Med 2004 Vol.

7 32, No. 9 (Suppl.)that are rapid, convenient, and InductionMethodologies: Surface andInternal CoolingEach method for inducing hypother-mia represents a different compromiseamong invasiveness, cooling rate, tem-perature control, and ease of use. Mini-mally invasive surface cooling techniquessuch as ice packs, forced-air cooling mat-tresses and blankets, and cooling capshave been used in clinical studies of pa-tients with cardiac arrest (8, 9, 11, 12). Inthe hypothermia After Cardiac Arreststudy, the median time from return ofspontaneous circulation to target coretemperature (32 34 C) was 8 hrs (inter-quartile range, 4 16 hrs), with typicalcooling rates of 1 C/hr (9). Some sur-face methods used in these studies re-quire minimal equipment ( , ice packs)and can be initiated by paramedics.

8 Oth-ers, such as cooling mattresses/blankets,require specialized cooling techniques such asendovascular cooling catheters have beendeveloped to address the induction,maintenance, and rewarming phases ofhypothermia. Such catheters have dem-onstrated rapid cooling rates in human-sized swine ( C/hr) and nonhumanprimates ( C/hr) (13, 14). Recently,the Cool-MI study utilized endovascularcooling catheters for inducing hypother-mia in awake, but sedated, patients in thesetting of acute ST-segment elevationmyocardial infarction (4). Although moreinvasive, this approach provides fastercooling rates and more precise tempera-ture control than surface cooling. Otherinternal cooling techniques reported in-clude the use of hemodialysis (15).

9 Internalcooling techniques provide faster cooling;however, some of this advantage is lost be-cause additional time is required for theset-up and placement of catheters and sup-port equipment before cooling is studies have demonstratedthat an intravenous bolus of chilled sin-gle-phase crystalloidfluid can quickly in-duce hypothermic core temperatures(16 19). infusion of a large-volume bolus(40 mL/kg) of chilled Saline via a femoralcatheter produced an average C de-crease in core temperature within ap-proximately 30 mins (17). One study ofcomatose out-of-hospital cardiac arrestsurvivors demonstrated an average Cdecrease in bladder temperature after abolus (30 mL/kg) of chilled (4 C) lactatedRinger s (given via peripheral or via cen-tral catheter).

10 In addition, the groupdemonstrated a significant increase inmean arterial pressure. Despite the largebolus volume, none of the postarrest pa-tients developed clinical or radiographicevidence of pulmonary edema (16).The cooling rates achieved by intrave-nous chilled Saline seem quite rapid, yet thelarge bolus volumes required to reach hy-pothermic temperatures remain a potentialconcern given the variation in cardiopul-monary dysfunction that may occur afterreturn of spontaneous circulation. In addi-tion to cardiac arrest, other resuscitationsettings may require high cooling potentialwith limitedfluid volumes. For example,recent strategies proposed for the treat-ment of hemorrhagic shock or traumaticbrain injury include the use of hypertonicsaline or the induction of mild hypother-mia.