The calcium paradox - What should we have to fear?

Oliveira, Marcos Aurélio Barboza de; Brandi, Antônio Carlos; Santos, Carlos Alberto dos; Botelho, Paulo Henrique Husseni; Cortez, Jose L.; Góissis, Gilberto; Braile, Domingo Marcolino

doi:10.5935/1678-9741.20140054

Cited by 4 publications

(4 citation statements)

References 42 publications

(58 reference statements)

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“…64-65 Similar studies demonstrated cell death after normalization of pH after cells were adapted to low pH conditions, as well as accelerated cell death upon reoxygenation (usually with room air 150 torr oxygen) of cells adapted to lowered oxygen levels. 66 It is now well accepted that cells grown in culture demonstrate the ability to die suddenly under the identical conditions that they once thrived in, if those baseline conditions are suddenly reintroduce after a period of metabolic deprivation or ischemia.…”

Section: Ischemia and Reperfusion/reperfusion Injurymentioning

confidence: 85%

Cardiac Arrest

2015

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The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The two primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation continue to evolve since they were established 60 years ago. The evolution of artificial circulation includes efforts to optimize manual CPR, external mechanical CPR devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the- counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a three phase model of treatment, newer approaches targeting patients who have suffered a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electrical activity, which is the presenting rhythm in at least one-third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level regarding ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a “cocktail” of multiple agents targeted at restoration of normal metabolism and prevention of reperfusion injury, as this holds the promise of restoring life to many patients for whom our current therapies fail.

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Section: Ischemia and Reperfusion/reperfusion Injurymentioning

confidence: 85%

Cardiac Arrest

2015

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“…Additionally, our study used PSM to balance important confounders when comparing outcomes. In prior studies by Nayler et al (21) and Oliveira et al (22), it is demonstrated that exposure of the myocardium to extracellular calcium in the postischemic reperfusion phase activates specific pathways that lead to a loss of cell structure/function (24). It is possible that the exposure of myocardial and neurologic tissues to IV boluses of calcium during arrest leads to an in vivo milieu of elevated extracellular calcium stores during the ischemic and reperfusion periods of CA, which may be detrimental to cellular function and recovery.…”

Section: Discussionmentioning

confidence: 99%

“…Because calcium can increase cardiac automaticity and contractility, children with HD frequently receive calcium during CPR (6,11,16). Studies describing effects of calcium on the myocardium exposed to prolonged ischemia show that increased levels of cytosolic calcium led to dissolution of the electrochemical gradient and a loss of osmotic control that results in cell lysis and death (20)(21)(22)(23)(24)(25)(26). Similar mechanisms may exist when calcium is administered during CPR in children, resulting in poor survival.…”

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confidence: 99%

Calcium Administration During Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest in Children With Heart Disease Is Associated With Worse Survival—A Report From the American Heart Association’s Get With The Guidelines-Resuscitation (GWTG-R) Registry*

Dhillon

Kleinman

Staffa

et al. 2022

Pediatric Critical Care Medicine

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IV calcium administration during cardiopulmonary resuscitation (CPR) for pediatric in-hospital cardiac arrest (IHCA) is associated with worse survival. We evaluated survival to hospital discharge in children with heart disease (HD), where calcium is more frequently administered during CPR. DESIGN:Retrospective study of a multicenter registry database. SETTING: Data reported to the American Heart Association's (AHA) Get With The Guidelines-Resuscitation registry. PATIENTS:Children younger than 18 years with HD experiencing an index IHCA event requiring CPR between January 2000 and January 2019. Using propensity score matching (PSM), we selected matched cohorts of children receiving and not receiving IV calcium during CPR and compared the primary outcome of survival to hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:We included 4,556 children with HD experiencing IHCA. Calcium was administered in 1,986 (44%), more frequently in children younger than 1 year old (65% vs 35%; p < 0.001) and surgical cardiac (SC) compared with medical cardiac patients (51% vs 36%; p < 0.001). Calcium administration during CPR was associated with longer duration CPR (median 27 min [interquartile range (IQR): 10-50 min] vs 5 min [IQR, 2-16 min]; p < 0.001) and more frequent extracorporeal-CPR deployment (25% vs 8%; p < 0.001). In the PSM cohort, those receiving calcium had decreased survival to hospital discharge (39% vs 46%; p = 0.02) compared with those not receiving calcium. In a subgroup analysis, decreased discharge survival was only seen in SC cohorts. CONCLUSIONS:Calcium administration during CPR for children with HD experiencing IHCA is common and is associated with worse survival. Administration of calcium during CPR in children with HD should be restricted to specific indications as recommended by the AHA CPR guidelines.

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“…1 The theory of the "calcium-paradox" as supported by the experimental settings, can further affect the myocardial function adversely. 4 The other concern regarding calcium administration in scenario of a pressure-overload hypertrophy emanates from the risk of "stone-heart" syndrome. 5 Moreover, calcium is believed to negatively interact with the concurrent catecholamines by attenuating the response to β-sympathomimetics.…”

Section: To the Editormentioning

confidence: 99%