Pulseless electrical activity following traumatic cardiac arrest: Sign of life or death?

BACKGROUND: Generally considered a sign of life, PEA is the most common arrhythmia encountered following pre-hospital traumatic cardiac arrest. Some recommend cardiac ultrasound (CUS) to determine cardiac wall motion (CWM) prior to terminating resuscitation efforts. This purpose of this study was to evaluate the outcomes of patients with traumatic cardiac arrest presenting with PEA, with and without CWM. METHODS: Trauma patients who underwent pre-hospital CPR were identified from the registries of two level-1 trauma centers. Pre-hospital management by emergency medical transport services was guided by advanced life support protocols. The on-duty trauma surgeon directed the resuscitations and performed or supervised CUS and determined CWM. RESULTS: Among 277 patients who underwent pre-hospital CPR, 110 patients had PEA on arrival to ED. 69 (62.7%) were injured by blunt mechanisms. Median CPR duration was 20.0 and 8.0 min for pre-hospital and ED, respectively. Sixty-three patients (22.7%) underwent resuscitative thoracotomy. One hundred seventy-two patients (62.1%) received CUS and of these 32 (18.6%) had CWM. CWM was significantly associated with survival to hospital admission (21.9% vs. 1.4%; P < 0.001); however, no patient with CUS survived to hospital discharge. Overall, only one patient with PEA on arrival survived to discharge. CONCLUSION: Following pre-hospital traumatic cardiac arrest, PEA on arrival portends death. Although CWM is associated with survival to admission, it is not associated with meaningful survival. Heroic resuscitative measures may be unwarranted for PEA following pre-hospital traumatic arrest, regardless of CWM.

Membrane attack complex generation increases as a function of time in stored blood.

OBJECTIVE: To determine if the complement system, a potent mediator of inflammation, contributes to haemolysis during red blood cell (RBC) storage. BACKGROUND: RBCs in storage undergo structural and biochemical changes that may result in adverse patient outcomes post-transfusion. Complement activation on leukodepletion and during storage may contribute to the RBC storage lesion. METHODS/MATERIALS: We performed a cross-sectional analysis of aliquots of leukoreduced RBC units, stored for 1-6 weeks, for the levels of C3a, C5a, Bb, iC3b, C4d and C5b-9 [membrane attack complex (MAC)] by enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed that only MAC levels significantly increased in RBC units as a function of storage time. We also observed that the level of C5b-9 bound to RBCs increased as a function of storage time. CONCLUSION: MAC levels increased over time, suggesting that MAC is the primary complement-mediated contributor to changes in stored RBCs. Inhibition of the terminal complement pathway may stabilise RBC functionality and extend shelf life.

The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage.

Carbon dioxide is perhaps the most potent available modulator of cerebrovascular tone and thus cerebral blood flow (CBF). These experiments evaluate the impact of induced hypercarbia on the matching of blood flow and metabolism in the injured brain. We explore the hypothesis that hypercarbia will restore the relationship of CBF to metabolic demand, resulting in improved outcome following traumatic brain injury (TBI) and hemorrhage. A behavioral outcome score, hemodynamic, metabolic, and pathologic parameters were assessed in anesthetized and ventilated juvenile pigs. Animals were assigned to either normocarbia or hypercarbia and subdivided into TBI (via fluid percussion) with or without hemorrhage. The experimental groups were TBI; TBI + 40% hemorrhage (40%H); TBI + hypercarbia (CO2); and TBI + 40%H + CO2. Hemorrhaged animals were resuscitated with blood and crystalloid. Hypercarbia was induced immediately following TBI using 10% FiCO2. The normocarbic group demonstrated disturbance of the matching of CBF to metabolism evidenced by statistically significant increases in cerebral oxygen and glucose extraction. Hypercarbic animals showed falls in the same parameters, demonstrating improvement in the matching of CBF to metabolic demand. Parenchymal injury was significantly decreased in hypercarbic animals: 3/10 hypercarbic versus 6/8 normocarbic animals showed cerebral contusions at the gray/white interface (p = 0.05). The hypercarbic group had significantly better behavioral outcome scores, 10.5, versus 7.3 for the normocarbic groups (p = 0.005). The decreased incidence of cerebral contusion and improved behavioral outcome scores in our experiments appear to be mediated by better matching of cerebral metabolism and blood flow, suggesting that manipulations modulating the balance of blood flow and metabolism in injured brain may improve outcomes from TBI.

Effect of unreamed, limited reamed, and standard reamed intramedullary nailing on cortical bone porosity and new bone formation.

OBJECTIVE: To compare the effects of unreamed nail insertion and reamed nail insertion with limited and standard canal reaming on cortical bone porosity and new bone formation. DESIGN: A canine segmental tibial fracture was created in fifteen adult dogs. The tibiae were stabilized with a statically locked 6.5-millimeter intramedullary nail without prior canal reaming (n = 5), after limited reaming to 7.0 millimeters (n = 5), or after standard canal reaming to 9.0 millimeters (n = 5). Porosity, new bone formation, and the mineral apposition rate of cortical bone were directly compared between the three nailing techniques. RESULTS: A significant increase in cortical bone porosity and new bone formation was seen in all three groups of experimental animals compared with the control tibiae. The overall lowest porosity levels were measured in the limited reamed group, with similar porosity levels measured in the unreamed and standard reamed groups. Porosity was lower in the limited reamed group in the entire cortex of the segmental and distal cross sections, as well as the endosteal, anterior, and posterior cortices along the length of the tibia. Overall, there was no difference in the amount of new bone formation or the mineral apposition rate between the three groups of animals at eleven weeks after surgery. DISCUSSION: The results of this study suggest that limited intramedullary reaming is a biologically sound alternative for the treatment of tibial diaphyseal fractures in which the circulation is already compromised.

Adverse sedation events in pediatrics: analysis of medications used for sedation.

OBJECTIVES: To perform a systematic investigation of medications associated with adverse sedation events in pediatric patients using critical incident analysis of case reports. METHODS: One hundred eighteen case reports from the adverse drug reporting system of the Food and Drug Administration, the US Pharmacopoeia, and the results of a survey of pediatric specialists were used. Outcome measures were death, permanent neurologic injury, prolonged hospitalization without injury, and no harm. The overall results of the critical incident analysis are reported elsewhere. The current investigation specifically examined the relationship between outcome and medications: individual and classes of drugs, routes of administration, drug combinations and interactions, medication errors and overdoses, patterns of drug use, practitioners, and venues of sedation. RESULTS: Ninety-five incidents fulfilled study criteria and all 4 reviewers agreed on causation; 60 resulted in death or permanent neurologic injury. Review of adverse sedation events indicated that there was no relationship between outcome and drug class (opioids; benzodiazepines; barbiturates; sedatives; antihistamines; and local, intravenous, or inhalation anesthetics) or route of administration (oral, rectal, nasal, intramuscular, intravenous, local infiltration, and inhalation). Negative outcomes (death and permanent neurologic injury) were often associated with drug overdose (n = 28). Some drug overdoses were attributable to prescription/transcription errors, although none of 39 overdoses in 34 patients seemed to be a decimal point error. Negative outcomes were also associated with drug combinations and interactions. The use of 3 or more sedating medications compared with 1 or 2 medications was strongly associated with adverse outcomes (18/20 vs 7/70). Nitrous oxide in combination with any other class of sedating medication was frequently associated with adverse outcomes (9/10). Dental specialists had the greatest frequency of negative outcomes associated with the use of 3 or more sedating medications. Adverse events occurred despite drugs being administered within acceptable dosing limits. Negative outcomes were also associated with drugs administered by nonmedically trained personnel and drugs administered at home. Some injuries occurred on the way to a facility after administration of sedatives at home; some took place in automobiles or at home after discharge from medical supervision. Deaths and injuries after discharge from medical supervision were associated with the use of medications with long half-lives (chloral hydrate, pentobarbital, promazine, promethazine, and chlorpromazine). CONCLUSIONS: Adverse sedation events were frequently associated with drug overdoses and drug interactions, particularly when 3 or more drugs were used. Adverse outcome was associated with all routes of drug administration and all classes of medication, even those (such as chloral hydrate) thought to have minimal effect on respiration. Patients receiving medications with long plasma half-lives may benefit from a prolonged period of postsedation observation. Adverse events occurred when sedative medications were administered outside the safety net of medical supervision. Uniform monitoring and training standards should be instituted regardless of the subspecialty or venue of practice. Standards of care, scope of practice, resource management, and reimbursement for sedation should be based on the depth of sedation achieved (ie, the degree of vigilance and resuscitation skills required) rather than on the drug class, route of drug administration, practitioner, or venue.

Adverse sedation events in pediatrics: a critical incident analysis of contributing factors.

OBJECTIVE: Factors that contribute to adverse sedation events in children undergoing procedures were examined using the technique of critical incident analysis. METHODOLOGY: We developed a database that consists of descriptions of adverse sedation events derived from the Food and Drug Administration's adverse drug event reporting system, from the US Pharmacopeia, and from a survey of pediatric specialists. One hundred eighteen reports were reviewed for factors that may have contributed to the adverse sedation event. The outcome, ranging in severity from death to no harm, was noted. Individual reports were first examined separately by 4 physicians trained in pediatric anesthesiology, pediatric critical care medicine, or pediatric emergency medicine. Only reports for which all 4 reviewers agreed on the contributing factors and outcome were included in the final analysis. RESULTS: Of the 95 incidents with consensus agreement on the contributing factors, 51 resulted in death, 9 in permanent neurologic injury, 21 in prolonged hospitalization without injury, and in 14 there was no harm. Patients receiving sedation in nonhospital-based settings compared with hospital-based settings were older and healthier. The venue of sedation was not associated with the incidence of presenting respiratory events (eg, desaturation, apnea, laryngospasm, approximately 80% in each venue) but more cardiac arrests occurred as the second (53.6% vs 14%) and third events (25% vs 7%) in nonhospital-based facilities. Inadequate resuscitation was rated as being a determinant of adverse outcome more frequently in nonhospital-based events (57.1% vs 2.3%). Death and permanent neurologic injury occurred more frequently in nonhospital-based facilities (92.8% vs 37.2%). Successful outcome (prolonged hospitalization without injury or no harm) was associated with the use of pulse oximetry compared with a lack of any documented monitoring that was associated with unsuccessful outcome (death or permanent neurologic injury). In addition, pulse oximetry monitoring of patients sedated in hospitals was uniformly associated with successful outcomes whereas in the nonhospital-based venue, 4 out of 5 suffered adverse outcomes. Adverse outcomes despite the benefit of an early warning regarding oxygenation likely reflect lack of skill in assessment and in the use of appropriate interventions, ie, a failure to rescue the patient. CONCLUSIONS: This study-a critical incident analysis-identifies several features associated with adverse sedation events and poor outcome. There were differences in outcomes for venue: adverse outcomes (permanent neurologic injury or death) occurred more frequently in a nonhospital-based facility, whereas successful outcomes (prolonged hospitalization or no harm) occurred more frequently in a hospital-based setting. Inadequate resuscitation was more often associated with a nonhospital-based setting. Inadequate and inconsistent physiologic monitoring (particularly failure to use or respond appropriately to pulse oximetry) was another major factor contributing to poor outcome in all venues. Other issues rated by the reviewers were: inadequate presedation medical evaluation, lack of an independent observer, medication errors, and inadequate recovery procedures. Uniform, specialty-independent guidelines for monitoring children during and after sedation are essential. Age and size-appropriate equipment and medications for resuscitation should be immediately available regardless of the location where the child is sedated. All health care providers who sedate children, regardless of practice venue, should have advanced airway assessment and management training and be skilled in the resuscitation of infants and children so that they can successfully rescue their patient should an adverse sedation event occur.

Secondary neurologic injury resulting from nonhypotensive hemorrhage combined with mild traumatic brain injury.

Although the emergency physician often treats patients with multiple injuries, there are relatively few clinically relevant models that mimic these situations. To describe the changes after a hemorrhagic insult superimposed on traumatic brain injury (TBI), anesthetized and ventilated juvenile pigs were assigned to 35% hemorrhage (35H), TBI (via fluid percussion); TBI + 35H, and TBI + 40H (40% hemorrhage). Animals were resuscitated with shed blood and crystalloid. Hemodynamic, metabolic, behavioral, and histologic parameters were assessed for 48 h. In TBI, mean arterial pressure (MAP) was not significantly different from baseline. For TBI + 40H, MAP fell by 60% (p < 0.05). This was corrected with resuscitation. Interestingly, TBI + 35H did not show a fall in MAP, while in 35H, MAP was reduced similarly to the TBI + 40H group. ICP was elevated only initially in the TBI group. In TBI + 40H and TBI + 35H, ICP increased markedly with resuscitation, remaining elevated for 60 min. ICP remained at baseline with 35 H. Hemorrhagic focal cerebal contusions at the gray-white interface were observed in 3/5 of TBI + 40H and 5/7 of TBI + 35H. Despite the presence of subarachnoid hemorrhage (SAH) in all the animals in the TBI alone group, none of these animals demonstrated grossly discernible intraparenchymal injury. There was no evidence of intracranial injury in the 35H group. Only in animals receiving a secondary insult of hemorrhage following the primary TBI were cerebral contusions found. These experiments demonstrate the evolution of cerebral contusions as a form of secondary neurologic injury following resuscitation from traumatic brain injury and hemorrhage, even in the absence of significant blood pressure changes.

Effect of dexamethasone on bovine airway smooth muscle cell proliferation.

Airway smooth muscle proliferation is a key component of airway wall remodelling that occurs as a consequence of inflammation in asthma. Studies were conducted to examine the effect of dexamethasone on airway smooth muscle cell (ASMC) proliferation in vitro. Dexamethasone (25-250 nM) significantly inhibited DNA synthesis and cell division induced by beta-hexosaminidase A (Hex A, 50 nM) in bovine ASMC. The inhibitory effect of dexamethasone on DNA synthesis was variable depending on the growth factors: significant effect was observed on Hex A and insulin; no significant effect was observed on epidermal growth factor and fetal bovine serum.

The relative importance of intramedullary, intracortical, and extraosseous soft-tissue blood flow to the repair of devascularized canine tibial cortex.

Previous studies have not quantified the relative contributions of intracortical and extracortical perfusion to cortical porosity and new bone formation. The current study was performed to determine the relative importance of intramedullary, intracortical, and extraosseous soft-tissue blood flow and type of tissue to the repair of devascularized canine tibial cortex. A 2.5-cm segment of tibia between two standardized osteotomies was devascularized. The segment was replaced anatomically and stabilized with a plate. The animals were divided randomly into two groups: skin coverage (N = 8) and muscle coverage (N = 8). Thirty-one days postoperatively, cerium141 microspheres were injected, prior to sacrifice, to measure blood flow. Extraosseous soft-tissue perfusion was the same in the skin coverage and muscle flap coverage groups. There was no relationship between intramedullary or extraosseous soft-tissue flow and depth of new bone formation and cortical porosity. Intracortical blood flow was directly related to depth of new bone formation (p = 0.0006) and cortical porosity (outer cortex, p = 0.001; inner cortex, p = 0.0001). These findings indicate that the cortical repair process is linked to the restoration of perfusion and that muscle coverage, rather than the quantity of blood flow, determines the extent of cortical repair.

Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by endotoxin.

To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was administered to anesthetized mongrel pigs 72 h following either hemorrhagic shock/resuscitation or sham shock. For TNF to be considered a mediator, at least two conditions should be satisfied: a TNF increase should precede other manifestations of the septic response and the magnitude of that increase should correlate with the symptoms. Immediately following resuscitation from shock, hemodynamics were stable, but heart rate, cardiac index (CI), and systemic oxygen delivery (DO2) were elevated 20-60%, and systemic vascular resistance (SVR) was decreased 40%, relative to the preshock baseline. After 72 h, the animals were reanesthetized, reinstrumented, and all hemodynamic values were near normal in both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) micrograms/kg of Escherichia coli LPS was administered intravenously over 30 min. Serial hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS. LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was followed by a hyperdynamic septic response (i.e., progressive arterial desaturation, tachypnea, tachycardia, increased CI, and decreased SVR) and rise in plasma TNF at 60-90 min. In the shock group, LPS-evoked TNF changes were less than or equal to those in the sham group, even though mortality was higher after shock.(ABSTRACT TRUNCATED AT 250 WORDS)

(--)-alpha-Acetylmethadol effects on alcohol and diazepam use, sexual function and cardiac function.

Selected behavioral and physiological effects of maintenance on (--)-alpha-acetylmethadol (LAAM) were examined for 67 men beginning LAAM maintenance. Thirty-four began LAAM maintenance after 1 month or more on methadone; 33 others were using street heroin immediately before beginning LAAM. Subjects were followed for 20 weeks on LAAM; assessment focused on changes in alcohol and diazepam use, sexual behavior and testicular function, and cardiovascular function. There was a trend toward increased alcoholism-related behaviors, but not consumption of alcohol, when on LAAM. Use of diazepam remained low. Subjects reported slightly enhanced sexual activity: reported number of ejaculations tended to increase, although interest in sexual activity remained constant. Semen volume values remained in the low normal range. In contrast to an earlier published report of reduced sperm motility in methadone and heroin users, normal motility was noted in this sample. The incidence of abnormal sperm morphology decreased from baseline to the end of the study. Cardiovascular function, as assessed by response to standard exercise, was unchanged during LAAM maintenance. Electrocardiograms revealed minor abnormalities prior to beginning LAAM maintenance; but these abnormalities did not consistently change during treatment. There is little evidence that the effects of LAAM maintenance differ from the effects of methadone maintenance on these behavioral and physiological functions.

Heroin addict responses to six weeks of detoxification with LAAM.

This paper describes the range of experience of 28 heroin addicts who received LAAM instead of methadone over six weeks in an outpatient detoxification program. Four patients are singled out to illustrate the variety of response during withdrawal, temporary abstinence from drugs, and social adjustment. The paper explores the motivation of patients and both their physical and subjective responses to the detoxification attempt. By describing a variety of patients, the paper documents clinical responses that cannot be communicated in statistical summaries or single-case reports. Overall, the cases illustrate the difficulties of brief-stay outpatient detoxification from heroin. Clinicians should expect to see only small steps toward rehabilitation during a patient's attempt to taper from opiates, but even minimal progress may justify the use of detoxification programs as a link between "street life" and the decision to enter long-term treatment.

Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone.

A randomized clinical trial compared four methods of outpatient withdrawal from heroin. Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate. Within each drug group, subjects were assigned to detoxification programs either within the standard three-week period or in an extended six weeks of treatment. Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up. Methadyl acetate performed similarly to methadone in most respects. Six-week withdrawal showed some temporary benefits over standard treatment, but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome.