RESUSCITATION
| PROS AND CONS OF FLUID RESUSCITATION —David H. Wisner, MD, Professor and Vice Chair, Department of
Surgery, University of California, Davis, School of Medicine, Sacramento, CA
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| Early resuscitation of injured patient: 2 approaches currently debated; traditional approach—administer ≈2 L
isotonic fluid fast via 2 large-bore intravenous (IV) lines; if no result, give additional ≈2 L; if no result, consider blood; if
still no response, surgery; proposed newer approach—takes view that pumping fluids increases (risk of) mortality by
raising intravascular volume; use of hypertonic fluid that will maintain a slightly hypotensive state and ultimately keep
intravascular volume, blood pressure (BP), and intracranial pressure (ICP) from increasing to cause a fatal hemorrhagic
event
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Animal Studies
| Crude models: rat tail vein—to simulate penetrating injury, cut off part of rat’s tail and let it bleed; amount of bleeding
depends on how much tail cut off; large vessel—hole made in aorta or iliac artery and allowed to bleed; most analogous
to injury to major vessel from gunshot or stab wound; can also do injuries to sites, eg, spleen, liver
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 | Tail vein study: 10 yr ago; investigated mortality rates in animals that got no resuscitation or ≈40 mL/kg normal saline; mortality
rate not significantly lower with resuscitation; however, could argue rat’s tail not analogous to human trauma
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| Alternative model: put piece of wire through anterior surface of aorta to create standard-size hole more like human injury;
bring wire to outside; after animal recovers from surgery, pull on wire to start bleeding
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| Bickell study using wire in pigs: if animals not resuscitated, all survived; when resuscitated (large resuscitation volume),
all died; conclusion negative for resuscitation; discovered that hole in aorta needed to be certain size; if hole too small,
all animals survived, if too big, all animals died; could conclude from this study that in pigs with just right-sized hole in
aorta from wire placed in laboratory, resuscitation bad; significantly more bleeding from resuscitated than from aortas
not resuscitated
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| University of California at Davis study: speaker’s team (focus 85% blunt trauma) replicated trauma to liver in rats;
looked at no resuscitation or IV lactated Ringer’s; no difference between 2 groups in mortality, although Ringer’s group bled
slightly more
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Human Studies
| Bickell et al: looked at penetrating-trauma patients (immediate group); half of patients had IV put in and resuscitated vigorously
in field using isotonic solution if systolic BP <90 mm/Hg (traditional resuscitation); therapy continued in emergency
department (ED); other half (delayed group) got heparin lock on semirandomized basis; in theory, not supposed to
receive any therapy until in operating room and bleeding under control, at which point they were resuscitated; study prospective,
controlled, semirandomized (odd/ even day), not blinded
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| Results: BP somewhat higher with immediate fluid resuscitation (expected); BP lower if not resuscitated (blood not diluted
as much, so hemoglobin (Hb) and platelet count higher and prothrombin time lower); outcome data—com--plication
rate lower, length of stay shorter, and mortality rate lower in group that just got heparin lock
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| Analysis: study heavily debated; argument study not truly randomized not relevant in speaker’s opinion; study involved
penetrating trauma only, so need to exercise care if applying to motor vehicle trauma
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| Important considerations: not all study patients went to surgery, and those who did spent almost 1 hr in ED; speaker thinks
delay too long, given average systolic BP in ED ≈70 mm/Hg; in speaker’s hospital, patients would get to operating room
faster; mortality rates higher than expected in control and experimental groups; in addition, protocol violations occurred in
which some patients not supposed to receive fluid given fluid; limitations—most importantly, study used post hoc or after-the-fact
reasoning, ie, statistical analysis included only patients who needed surgery; this produced statistical significance
not found when all patients included; study concludes patient with gunshot or stab wound to chest or belly who is
hypotensive in field and in need of surgery should not receive volume; however, whether patient will need surgery not
known in field or when patients arrive in ED
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| Additional data: from same cohort; retrospectively looked at which kinds of injuries derived survival benefit from not being
resuscitated; vascular injuries (analogous to pigs with hole in anterior aorta), no difference in survival with resuscitation;
solid organ injuries (analogous to rats), no difference; all thoracic injuries taken together, no difference; but in
cardiac injuries, ≈50% reduction in mortality when not resuscitated; speaker concludes that in case of gunshot or stab
wound to heart, vigorous fluid resuscitation may be harmful; protective tamponade by way of concurrent hole in pericardium
provides possible explanation
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| Cochrane Collaboration: in recent meta-analysis, addressed question of early resuscitation compared to delayed resuscitation
and whether small- or large-volume resuscitation better; concluded no evidence for or against early or larger-
volume IV resuscitation in uncontrolled hemorrhage (which speaker concludes reflects current debate)
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| Conclusion: no set answer as to which approach better; best approach to take now may be concept of “responders” used
by Advanced Trauma Life Support (ATLS), ie, give arriving patients volume; if no response, move to aggressive therapy
for hemorrhage (surgery or, if pelvic fracture present, interventional radiology)
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| FLUIDS, BLOOD, AND ARTIFICIAL HEMOGLOBIN IN TRAUMA — Carlos V.R. Brown, MD, Assistant Professor of
Surgery, Keck School of Medicine at the University of Southern California, Los Angeles, and Los Angeles County-USC
Medical Center
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| Hypertonic saline: osmolarity of normal saline 0.9% ≈300 mOsm/L; hypertonic saline 1.7% to 29%; most commonly
used 3%, 5%, and 7.5%; usually given with additive (6% dextran-70 most common) and as bolus (≈4 mL/kg, which
adds up to ≈250 mL [for 70-kg man]); keep in mind serum sodium and serum chloride increase during resuscitation;
chloride side effect that causes acidosis
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| Cardiovascular effects: increases mean arterial pressure through volume expansion and osmotic shift; increases cardiac
output; causes vasodilation due to decreased endothelial edema and release of relaxing factor
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| Neurologic effects: decreases ICP via cellular dehydration, which is key potential benefit for trauma therapy (resuscitation);
improves cerebral blood flow; increases cerebral perfusion pressure (CPP); increased mean arterial pressure and
decreased ICP amount to “ideal medication for head injury”; also better gas exchange in lungs; natriuresis from kidneys;
immunomodulatory effects
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| Study: article in Annals of Surgery randomized patients with traumatic hemorrhagic shock to receive hypertonic saline
or normal saline; found blunted immune response in hypertonic saline group, which may help prevent multisystem organ
failure in humans as in animals
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| ICP: studies show hypertonic saline decreases ICP; studies of resuscitation comparing hypertonic saline to crystalloid solution
with no additive show results about same in trauma, burns, and surgery; hypertonic saline with dextran same as
normal saline
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| Summary on hypertonic saline: know hospital’s stock; may need to mix; increases BP and cardiac output; decreases ICP;
appears as safe as isotonic fluid (normal saline); subgroups may benefit (eg, head-injured hypotensive patients); studies
by Resuscitation Outcomes Consortium (ROC) will provide more information
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| Albumin: Saline vs Albumin Fluid Evaluation (SAFE) trial (2004)—≈7000 patients receiving intensive care unit
(ICU) resuscitation randomized to albumin or saline; no difference in mortality; subgroup analysis showed trauma patients
had slightly higher mortality than albumin group (14% vs 10%); patients with sepsis seemed to have lower mortality
with albumin; caution urged for albumin use, at least early on in trauma
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| Anemic patients: separate population from bleeding patients; need adjustments in care, eg, drawing pediatric tubes,
drawing blood less often or not at all, possibly erythropoietin; do not routinely need blood
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| Blood transfusion: Hebert et al (1999)—prospective trial; 838 ICU patients randomized to liberal group (transfused if
Hb 10-12 g/dL) or restrictive group (transfused if Hb 7-9 g/dL); no difference in mortality, although trend toward improved
mortality in restricted group; in subgroup analysis of 203 trauma patients (103 liberal; 103 restrictive), mortality
10% in both groups
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| Artificial Hb: diaspirin crosslinked Hb (HemeAssist)—pro--mising animal studies, but clinical trials in humans in
1990s showed significantly higher mortality; study terminated; human recombinant Hb — phase 1 and 2 trials; serious
side effects included vasoconstriction and pulmonary hypertension; free-form Hb potent vasoconstrictor that causes damage
to kidneys and liver; development ceased in 2003; bovine polymerized Hb (Hemopure)— currently approved for
use in South Africa; side effects seen in phase 3 trials include increased BP, decreased cardiac index, elevated amylase,
lipase, creatinine, and liver function tests, indicating end-organ damage; benefits of artificial Hb—stored at room temperature;
shelf life ≤36 mo; universal compatibility; immediate oxygen delivery; processed to remove infectious agents
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| Derivatives of human Hb: human polymerized Hb (PolyHeme)—Hb polymerized from outdated donor red blood
cells; 2002 trial compared Polyheme recipients with patients who did not receive blood for religious reasons; PolyHeme
group did much better; currently awaiting results of phase 3 prehospital multicenter randomized trial; human conjugated
Hb—maleimide activated polyethylene glycol-conjugated human Hb (MP4); may cause less vasoconstriction; animal
studies only
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| NEW FRONTIERS IN CPR: BACK TO BASICS —Daniel Davis, MD, Associate Professor of Medicine, University of
California, San Diego, School of Medicine
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| Ventricular fibrillation (VF): new model of VF relevant to all cardiac arrests and all resuscitations; first 4 min electrical
phase; 4 to 10 min circulatory phase; >10 min metabolic phase; ideal treatment still shock in first phase; in circulatory
phase, cardiopulmonary resuscitation (CPR) first
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| CPR’s priming effect: increases chance of resuscitation success; after 90 sec of CPR, VF wave form similar to original,
indicating CPR prepares heart for successful defibrillation; to adequately prime heart, must reach threshold coronary perfusion
pressure (CPP) and sustain it for 2 to 3 min; priming effect lost in seconds; 3 most influential animal studies looked at
whether to shock first or do compressions first; whether 5 min, 8 min, or 10 min of VF, found far better to do CPR before
shock in all groups; animals shocked as first treatment did worse
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| CPR-first approach studied: out-of-hospital data on humans (Seattle); before 1990, emergency medical technicians
(EMTs) started compressions before ambulance arrived with defibrillator; when automatic emergency defibrillators
(AEDs) used by EMTs and shock delivered as soon as possible, period of CPR before defibrillation eliminated, and survival
rates declined; in 1994, current approach adopted, ie, 90 sec CPR first, even when shockable rhythm present
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| Bystander CPR: patients known to do better; studied in San Diego where no CPR-first approach (few locations in world
have CPR-first); looked at patients ≤4 min vs ≥4 min in arrest state; found if patient in arrest ≤4 min, no survival difference
if bystander CPR performed, but if arrest time ≥4 min without bystander CPR, chance of survival 0
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| Adjunct to priming effect: pig study—induced VF in pigs; waited 8 min; gave shock first or CPR-first or CPR-first
plus ≥1 drugs (propranolol, lidocaine, bretyllium, U-74389 G [lazaroid; free radical scavenging agent], epinephrine, or all
of these); found 1-hr survival with shock first 12% to 13%, with CPR-first, survival almost double; adding other drugs
did not have much effect, although response rate with free radical scavenger good (≈40%) and with epinephrine >60%;
added up to 100% survival; indicates CPR period window for administering drugs and boosting survival and outcome
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| Other indicators: delay between CPR and shock—2 groups of pigs had VF induced, then CPR started in ≈2 min; one
group received defibrillation right after CPR; other group waited ≈20 to 30 sec (best possible delay between CPR and
defibrillation); in group defibrillated without delay, sudden rise in aortic pressure indicated return of spontaneous circulation
at rate 5 times higher than in group with delay; no evidence of this in humans yet
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| Chest recoil: new concept; CPR developed from core idea of open cardiac massage and compressing heart between sternum
and backbone; new approach treats entire chest, notably lungs, as “giant heart” that fills with blood with each
compression (heart itself circulates relatively smaller volume); however, air from mouth competes with blood for lung
space (probably do not need 100 breaths/min)
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| Impedance threshold device (ITD): addresses air problem; consists of rubber diaphragm that sits over port attached to
endo-tracheal tube and stops air from rushing in during compressions
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| Ventilation: currently, may be ventilating too fast and hurting patients; dropping PCO 2 detrimental, especially to brain;
in San Diego trauma patients, outcomes better in therapeutic range of PCO 2 30 to 50 mm Hg; worst ventilation speaker
sees is by hospital respiratory therapists (RTs); retrain RTs and alert physicians and nursing staff; injured brain — as
soon as PCO 2 <≈27 mm Hg or pH allowed to rise, cells polarize; mediators of injury; neurons “hate” hypocapnea; may
play significant role in outcomes for head injury in field
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| Injurious vs noninjurious ventilation: injurious ventilation (10 to 12 mL/kg) for each tidal volume without positive
end-expiratory pressure (PEEP); lung protective ventilation (5 to 7 mL/kg) with PEEP; important due to effect of ventilation
on immune system; within first 30 to 60 min, rapid rise in cyto-kines in plasma; injurious ventilation same as standard
ventilation by EMTs
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| Take-home messages: make CPR priority; minimize delay to shock; slow ventilation rate (<12/min); new technology
may help decrease hypoxic arrests
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Educational Objectives
| The goal of this program is to educate the listener about fluid resuscitation, fluid alternatives, and developments in cardiopulmonary
resuscitation (CPR). After hearing and assimilating this program, the clinician will be better able to:
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| 1. Name 2 distinct approaches to fluid resuscitation.
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| 2. Cite results of an important human study of penetrating injury and fluid resuscitation.
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| 3. List and discuss some alternatives to lactated Ringer’s solution for the fluid resuscitation of trauma patients.
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| 4. Discuss the priming effect of CPR in successful defibrillation.
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| 5. Discuss optimal ventilation rates and the concept of injurious vs noninjurious ventilation.
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Discussed On This Program
Epinephrine [Adrenalin Chloride, Adrenalin Chloride Solution, Epifrin]
Lidocaine (several trade names and formulations)
Propranolol HCl [Inderal, Inderal LA, InnoPran XL]
Bretyllium (no longer available)
U-74389G (lazaroid)
Suggested Reading
Boldt J et al: The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing
major abdominal surgery. Anesth Analg 103:191, 2006; Boldt J: Fluid choice for resuscitation of the trauma patient: a review
of the physiological, pharmacological, and clinical evidence. Can J Anaesth 51:500, 2004; Dubick MA et al: Issues
of concern regarding the use of hypertonic/hyperoncotic fluid resuscitation of hemorrhagic hypotension. Shock
25:321, 2006; Dunne JR et al: Blood transfusion is associated with infection and increased resource utilization in combat
casualties. Am Surg 72:619, 2006; Dunne JR et al: Blood transfusion is associated with infection and increased resource
utilization in combat casualties. Am Surg 72:619, 2006; Guterman L: Artificial-blood study has critics seeing
red. Chron High Educ 52:A17, 2006; Horton JW et al: Hypertonic saline dextran after burn injury decreases inflammatory
cytokine responses to subsequent pneumonia-related sepsis. Am J Physiol Heart Circ Physiol 290:H1642, 2006;
Epub 2005 Nov 18. Kaakinen T et al: Hypertonic saline dextran improves outcome after hypothermic circulatory arrest:
a study in a surviving porcine model. Ann Thorac Surg 81:183, 2006; Kreimeier U et al: Small-volume resuscitation:
from experimental evidence to clinical routine. Advantages and disadvantages of hypertonic solutions. Acta
Anaesthesiol Scand 46:625, 2002; Kwan I et al: Timing and volume of fluid administration for patients with bleeding.
Cochrane Database Syst Rev:CD002245, 2003; Leppaniemi AK: Abdominal war wounds--experiences from Red
Cross field hospitals. World J Surg29 Suppl 1:S67, 2005; Mizushima Y et al: Fluid resuscitation of trauma patients:
how fast is the optimal rate? Am J Emerg Med 23:833, 2005; Ohshige K et al: Evaluation of out-of-hospital cardiopulmonary
resuscitation with resuscitative drugs: a prospective comparative study in Japan. Resuscitation 66:53, 2005; Ornato
JP et al: Prehospital and emergency department care to preserve neurologic function during and following
cardiopulmonary resuscitation. Neurol Clin 24:23, 2006; Rosenberg M: American Heart Association changes CPR
guidelines. J Mass Dent Soc 55:36, 2006; Salomone JP et al: Opinions of trauma practitioners regarding prehospital
interventions for critically injured patients. J Trauma 58:509, 2005; Spencer KW: Updates to the American Heart Association
CPR guidelines. Plast Surg Nurs 26:5, 2006; Twomley KM et al: Proinflammatory, immunomodulating, and
prothrombotic properties of anemia and red blood cell transfusions. J Thromb Thrombolysis 21:167, 2006; Watters JM
et al: A single bolus of 3% hypertonic saline with 6% dextran provides optimal initial resuscitation after uncontrolled hemorrhagic
shock. J Trauma 61:75, 2006; Wesley AK: Improving the hemodynamics of CPR. AHA guidelines support
timely and effective CPR. Emerg Med Serv 35:82, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Drs. Wisner and Brown spoke at the California Trauma Conference held in San Diego, CA, January 26-28, 2006, and
sponsored by the University of California at San Diego, Los Angeles, Davis, San Francisco, and Fresno, as well as by
Scripps Mercy Hospital, Scripps Memorial Hospital, Sharp Memorial Hospital, Palomar Medical Center, and Children’s
Hospital of San Diego. Dr. Davis spoke at the Critical Care meeting in San Diego, CA, held July 21-23, 2005, and sponsored
by the University of California, San Diego, School of Medicine. The Audio-Digest Foundation thanks the speakers
and the sponsors for their cooperation in the production of this program.
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