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- Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model. [JOURNAL ARTICLE]
- Cryobiology 2014 Sep 12.
Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming.A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: 1) A normothermic group receiving Milrinone, 2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and 3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle.After rewarming from 15°C, stroke volume, cardiac output and total peripheral resistance returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls.Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation.
- Hypothermia in Victims of the Great East Japan Earthquake: A Survey in Miyagi Prefecture. [JOURNAL ARTICLE]
- Disaster Med Public Health Prep 2014 Sep 12.:1-11.
A survey was conducted to describe the characteristics of patients treated for hypothermia after the Great East Japan Earthquake.Written questionnaires were distributed to 72 emergency medical hospitals in Miyagi Prefecture. Data were requested regarding inpatients with a temperature less than 36ºC admitted within 72 hours after the earthquake. The availability of functional heating systems and the time required to restore heating after the earthquake were also documented.A total of 91 inpatients from 13 hospitals were identified. Tsunami victims comprised 73% of the patients with hypothermia. Within 24 hours of the earthquake, 66 patients were admitted. Most patients with a temperature of 32ºC or higher were treated with passive external rewarming with blankets. Discharge without sequelae was reported for 83.3% of patients admitted within 24 hours of the earthquake and 44.0% of those admitted from 24 to 72 hours after the earthquake. Heating systems were restored within 3 days of the earthquake at 43% of the hospitals.Hypothermia in patients hospitalized within 72 hours of the earthquake was primarily due to cold-water exposure during the tsunami. Many patients were successfully treated in spite of the post-earthquake disruption of regional social infrastructure.(Disaster Med Public Health Preparedness. 2014;0:1-11).
- Is enteral feeding tolerated during therapeutic hypothermia? [JOURNAL ARTICLE]
- Resuscitation 2014 Sep 2.
To determine whether patients undergoing therapeutic hypothermia following cardiac arrest tolerate early enteral nutrition.We undertook a single-centre longitudinal cohort analysis of the tolerance of enteral feeding by 55 patients treated with therapeutic hypothermia following resuscitation from cardiac arrest. The observation period was divided into three phases: (1) 24h at target temperature (32-34°C); (2) 24h rewarming to 36.5°C; and (3) 24h maintained at a core temperature below 37.5°C.During period 1, patients tolerated a median of 72% (interquartile range (IQR) 68.7%; range 31.3 to 100%) of administered feed. During period 2 (rewarming phase), a median of 95% (IQR 66.2%; range 33.77 to 100%) of administered feed was tolerated. During period 3 (normothermia) a median of 100% (IQR 4.75%; range 95.25 to 100%) of administered feed was tolerated. The highest incidence of vomiting or regurgitation of feed (19% of patients) occurred between 24-48h of therapy.Patients undergoing therapeutic hypothermia following cardiac arrest may be able to tolerate a substantial proportion of their daily nutritional requirements. It is possible that routine use of prokinetic drugs during this period may increase the success of feed delivery enterally and this could usefully be explored.
- Remote ischemic preconditioning is a safe adjuvant technique to myocardial protection but adds no clinical benefit after on-pump coronary artery bypass grafting. [Journal Article]
- Heart Surg Forum 2014 Aug; 17(4):E220-3.
To evaluate the impact of remote ischemic preconditioning (RIPC) on clinical outcome, biological markers of myocardial injury, and its safety in patients undergoing on-pump coronary artery bypass grafting (CABG).This study was conducted at Ch. Pervaiz Elahi Institute of Cardiology (CPEIC) in Multan. The study took place from March 2012 to June 2013. Patients were randomly placed into two groups. Group A (N = 32) did not undergo RIPC; Group B (N = 35) received RIPC after induction of anesthesia. Similar standard general anesthesia, cardiopulmonary technique, myocardial protection strategies, and surgical techniques were used in both groups except the protocol for RIPC. Following postoperative outcome, i.e. cardiac defibrillation after removal of aortic cross clamp during the period of rewarming, demand for intra-aortic balloon pump (IABP), demand for antiarrhythmic before leaving the operation room, postoperative creatine kinase-myocardial band (CK-MB) level (at 1h, 12h, 24h, and 48h after surgery), postoperative serum creatinine level on first postoperative day, postoperative ejection fraction (EF) on third postoperative day, in-hospital mortality, and one-year mortality were noted, prospectively. Safety of protocol of RIPC was estimated by limb ischemia monitored by pulse oximetry during and after procedure of RIPC and postoperative neurapraxia by nerve examination of right upper limb.Post aortic cross clamp release cardiac defibrillation, demand for IABP, demand for high inotropes, and use of antiarrhythmic in the operation room were statistically insignificant in the non-RIPC and RIPC group with P values of .54, .78, .16, and .16, respectively. Mean postoperative CK-MB level (IU/L) showed the following results: At 1h (Group A 20.94 + 1.66, Group B 20.57 + 1.54, P = .35), at 12h (Group A 27.13 + 1.85, Group B 28.05 + 3.04, P = .135), at 24h (Group A 27.63 + 1.7, Group B 27.85 + 2.2, P = .63), and at 48h (Group A 22.95 + 2.76, Group B 23.27 + 3.6, P = .69). First postoperative day serum creatinine (Group A 1.29 + 0.395, Group B 1.33 + 0.57, P = .77) and postoperative ejection fraction percentage on the third postoperative day (Group A 50.78 + 8.72, Group B 50.57 + 8.38, P = .92) showed no statistical difference between two groups. Postoperative low cardiac output state, in-hospital mortality, and one-year mortality also were statistically insignificant between the groups with P values of .93, .29, and .33, respectively. None of the patients in either group showed evidence of limb ischemia and neurapraxia of the right upper limb.RIPC is a safe technique, but it does not have additional clinical benefit after on-pump CABG surgery in the presence of a standard myocardial protective strategy.
- Apparent Diffusion Coefficient Scalars Correlate with Near-Infrared Spectroscopy Markers of Cerebrovascular Autoregulation in Neonates Cooled for Perinatal Hypoxic-Ischemic Injury. [JOURNAL ARTICLE]
- AJNR Am J Neuroradiol 2014 Aug 28.
Neurologic morbidity remains high in neonates with perinatal hypoxic-ischemic injury despite therapeutic hypothermia. DTI provides qualitative and quantitative information about the microstructure of the brain, and a near-infrared spectroscopy index can assess cerebrovascular autoregulation. We hypothesized that lower ADC values would correlate with worse autoregulatory function.Thirty-one neonates with hypoxic-ischemic injury were enrolled. ADC scalars were measured in 27 neonates (age range, 4-15 days) in the anterior and posterior centrum semiovale, basal ganglia, thalamus, posterior limb of the internal capsule, pons, and middle cerebellar peduncle on MRI obtained after completion of therapeutic hypothermia. The blood pressure range of each neonate with the most robust autoregulation was identified by using a near-infrared spectroscopy index. Autoregulatory function was measured by blood pressure deviation below the range with optimal autoregulation.In neonates who had MRI on day of life ≥10, lower ADC scalars in the posterior centrum semiovale (r = -0.87, P = .003, n = 9) and the posterior limb of the internal capsule (r = -0.68, P = .04, n = 9) correlated with blood pressure deviation below the range with optimal autoregulation during hypothermia. Lower ADC scalars in the basal ganglia correlated with worse autoregulation during rewarming (r = -0.71, P = .05, n = 8).Blood pressure deviation from the optimal autoregulatory range may be an early biomarker of injury in the posterior centrum semiovale, posterior limb of the internal capsule, and basal ganglia. Optimizing blood pressure to support autoregulation may decrease the risk of brain injury in cooled neonates with hypoxic-ischemic injury.
- Frostbite of the hand. [Journal Article]
- J Hand Surg Am 2014 Sep; 39(9):1863-8.
Frostbite is damage caused by the freezing of tissue owing to exposure to extreme cold. Clinically, it is often difficult to identify the severity of frostbite injury. There may be a wide discrepancy between the extent of damage to the skin versus that to the deeper structures. The initial clinical impression is usually worse than actual tissue damage. In addition to physical examination, diagnostic imaging, especially triple-phase bone scan, has been proposed to help differentiate between superficial and deep damage. Principles of treatment involve rapid rewarming to thaw the tissues and halt direct cellular damage, methods to minimize progressive dermal ischemia, and active wound care to promote timely healing. Pharmacological adjuncts, such as fibrinolytics, have been proposed to minimize tissue damage. Surgical therapy is postponed until there is clear demarcation between healthy and necrotic tissue.
- Reversible deactivation of higher order posterior parietal areas I: Alterations of receptive field characteristics in early stages of neocortical processing. [JOURNAL ARTICLE]
- J Neurophysiol 2014 Aug 20.:jn.00140.2014.
Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L, 7b and motor/premotor cortex (M1/PM) using microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and non-human primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects, and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5-22 minutes of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex.
- Changes in cardiac thrombomodulin and heat shock transcription factor 1 expression and peripheral thrombomodulin and catecholamines during hypothermia in rats. [JOURNAL ARTICLE]
- Stress 2014 Aug 11.:1-27.
Abstract Effects of hypothermia and rewarming on thrombomodulin, catecholamines and heat shock transcription factor 1 (HSF1) were studied in rats. The aims of the study were to clarify whether cold stress, under anaesthesia, is sufficient to change levels of thrombomodulin in healthy endothelium and in the circulation, and whether adrenaline, noradrenaline and HSF1 could act as regulators in the process. Rats were divided into control, mild hypothermia (2 and 4.5 hours at +21(o)C; MH1, MH2), severe hypothermia (2 and 4.5 hours at +10(o)C; SH1, SH2) and two rewarming groups (2 hours at +10(o)C followed by 2 hours at +21(o)C or 3 hours at +28(o)C; SHW1, SHW2) (n=15/group, except n=6 in MH1). Fentanyl-fluanisone-midazolam was used as anesthetic. Low levels of thrombomodulin in plasma and myocardial arterioles/venules measured by ELISA and immunohistochemistry were associated with significant increase of thrombomodulin transcript level in SH1 rats analyzed by quantitative PCR. Plasma adrenaline correlated negatively with the relative amount of myocardial thrombomodulin transcripts and positively with plasma thrombomodulin in severe hypothermia. Transcript levels of thrombomodulin and HSF1 correlated strongly (r = 0.83; P <0.001) in severe hypothermia. Plasma/urine ratio of thrombomodulin and plasma adrenaline (r = 0.87; P = 0.005) or noradrenaline (r = 0.78; P = 0.023) were strongly correlated in SHW1 rats. Hence cellular and soluble levels of thrombomodulin are modified by cold stress in healthy rats, possibly via catecholamines and HSF1.
- Prolonged mild therapeutic hypothermia versus fever control with tight hemodynamic monitoring and slow rewarming in patients with severe traumatic brain injury: a randomized controlled trial. [JOURNAL ARTICLE]
- J Neurotrauma 2014 Aug 6.
Although mild therapeutic hypothermia is an effective neuroprotective strategy for cardiac arrest/resuscitated patients, and asphyxic new-borns, recent randomized controlled trials (RCTs) have equally shown good neurological outcome between targeted temperature management at 33°C versus 36°C and have not shown consistent benefits in patients with traumatic brain injury (TBI). We aimed to determine the effect of therapeutic hypothermia while avoiding some limitations of earlier studies, which include patient selection based on Glasgow coma scale (GCS), delayed initiation of cooling, short duration of cooling, inter-center variation in patient care, and relatively rapid rewarming. We conducted a multicenter RCT in patients with severe TBI (GCS 4-8). Patients were randomly assigned (2:1 allocation ratio) to either therapeutic hypothermia (32-34°C, n = 98) or fever control (35.5-37°C, n =50). Patients with therapeutic hypothermia were cooled as soon as possible for ≥ 72 h and rewarmed at a rate of < 1°C/day. All patients received tight hemodynamic monitoring under intensive neurological care. The Glasgow Outcome Scale was assessed at 6 months by physicians who were masked to the treatment allocation. The overall rates of poor neurological outcomes were 53% and 48 % in the therapeutic hypothermia and fever control groups, respectively. There were no significant differences in the likelihood of poor neurological outcome (relative risk [RR] 1.24, 95% confidence interval [CI] 0.62-2.48, p =0.597) or mortality (RR 1.82, 95% CI 0.82-4.03, p =0.180) between the two groups. We concluded that tight hemodynamic management and slow rewarming, together with prolonged therapeutic hypothermia (32-34°C) for severe TBI, did not improve the neurological outcomes or risk of mortality compared with strict temperature control (35.5-37°C).
- Pediatric submersion injuries: emergency care and resuscitation. [Journal Article]
- Pediatr Emerg Med Pract 2014 Jun; 11(6):1-21; quiz 21-2.
Drowning and submersion injuries are highly prevalent, yet preventable, causes of childhood mortality and morbidity. Although much of the resuscitation of the drowning pediatric victim is basic to all respiratory and cardiac arrest situations, there are some caveats for treatment of this type of injury. Risk factors for drowning victims include epilepsy, underlying cardiac dysrhythmias, hyperventilation, hypoglycemia, hypothermia, and alcohol and illicit drug use. Prehospital care should focus on restoring normal ventilation and circulation as quickly as possible to limit the extent of hypoxic insult. Diagnostic testing for symptomatic patients may include blood glucose level, arterial blood gas level, complete blood count, electrolytes levels, chest radiography, and cardiorespiratory monitoring with pulse oximetry and a rhythm strip. In this review, passive external, active external, and active internal rewarming techniques for treatment of hypothermic patients are discussed. A systematic approach to treatment and disposition or admission of pediatric drowning victims is also included, with extensive clinical pathways for quick reference.