Intrastate Variation in Treatment and Outcomes of Out-of-Hospital Cardiac Arrest.

OBJECTIVE: Our objective was to analyze and compare out-of-hospital cardiac arrest (OHCA) system of care performance and outcomes at the Medical Control Authority (MCA) level in the state of Michigan. We hypothesized that clinically and statistically significant variations in treatment and outcomes of OHCA exists within a single U.S. state. METHODS: We performed a retrospective, observational study of all non-traumatic EMS-treated OHCA from the state of Michigan CARES registry for 2014-2015. Geocoding of the OHCA incident address was used to assign records to individual MCAs. MCA-based demographics, arrest characteristics, system of care performance and outcomes were quantified and compared. Associations between demographics, system of care parameters, and outcomes were examined at the MCA level. RESULTS: A total of 8,115 records with complete data were available for analysis. Eleven MCAs met study inclusion criteria of >100 cases, producing a final sample size of 7,788 records (96%). Statistically significant variations in survival to hospital discharge ranged from 4.5% to 15% (p < 0.001) (Adjusted odds ratio [AOR] range 0.6-2.0) and survival with good neurologic outcome 2.7-12.5% (p < 0.001; AOR range 0.5-2.2,) were observed across MCAs. Bystander CPR ranged from 32% to 53% (p < 0.001) and bystander AED application ranged from 3.5% 11.5% (p < 0.05). Of patients admitted to the hospital alive, 29-68% received targeted temperature management. In hospital mortality ranged from 53.1% to 73.9% (p < 0.05). CONCLUSION: Significant intrastate variability in OHCA system of care performance and outcomes currently exist and are similar to what has been previously reported across North America almost a decade ago. This degree of variability highlights the opportunity to optimize modifiable factors within local systems of care to improve OHCA outcomes.

Protein synthesis inhibition as a potential strategy for metabolic down-regulation.

OBJECTIVE: This pilot study tested the potential of puromycin (PUR) to inhibit protein synthesis and reduce oxygen utilization in a non-hibernating, whole animal preparation. METHODS: After anesthesia and instrumentation, male rats received a single dose of PUR or 0.9% saline (control), followed 60 min later with [(35)S] methionine/cysteine radiolabeling. Thirty minutes after isotope injection, organ biopsies were taken for quantification of de novo protein synthesis. Arterial and central venous blood gases were obtained at baseline and 60 min after injection of PUR or 0.9% saline. Temperature, mean arterial pressure (MAP), and heart rate were recorded continuously. RESULTS: Animals receiving PUR demonstrated significant reductions in protein synthesis in all organ systems sampled (p<0.05). The overall reduction averaged 67.8%. Central venous oxygen saturations (S(cv)O(2)) were higher in the PUR group than the controls at 60 min (90+/-2% versus 80+/-4%, p<0.05). The oxygen extraction ratio (O(2)ER) decreased from 16.1+/-1.7% to 6.8+/-1.2% in the PUR group (p<0.05) and increased from 12.5+/-3.2% to 16.0+/-4.2% in the controls (p=0.44). There was no difference in temperature, MAP, heart rate or blood gas variables, other than S(cv)O(2), at baseline or 60 min between groups. CONCLUSIONS: These results demonstrate that PUR is capable of reducing whole body protein synthesis significantly within a relatively short duration of time. This appears to decrease whole body oxygen utilization as evidenced by an increase in S(cv)O(2) and a decrease in O(2)ER. Protein synthesis inhibition may reduce metabolic demands and should be tested for its potential to improve outcomes where oxygen demands exceed oxygen delivery.

Comparison of a new hemostatic agent to current combat hemostatic agents in a Swine model of lethal extremity arterial hemorrhage.

BACKGROUND: Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model has demonstrated that QuikClot zeolite granules (QCG) and the HemCon chitosan bandage (HC) are not capable of providing hemostasis and improving survival over the Army gauze field bandage (AFB). We have developed a new hemostatic agent consisting of a granular combination of a smectite mineral and a polymer (WoundStat) capable of producing hemostasis in the face of high-pressure arterial bleeding. We compared the performance of WoundStat (WS) to QCG, HC, AFB, and the new QuikClot zeolite Advance Clotting Sponge (ACS) in a lethal vascular injury model. METHODS: Hemostatic agents were tested using a lethal femoral artery vascular injury model. Twenty-five (5 per group) male swine (42 kg +/- 3 kg) were anesthetized, instrumented, and splenectomized. A lethal femoral artery injury was produced by creating a 6-mm arteriotomy in the vessel. After 45 seconds of hemorrhage, animals were randomized to be treated with AFB (control group), HC, QCG, ACS, or WS. Pressure (200 mm Hg) was applied over the product in the wound for 3 minutes. A second application and 3 additional minutes of pressure was provided if hemostasis was not achieved. Fluid resuscitation was begun at the time of application with 500 mL of Hextend, followed by lactated Ringer's solution at 100 mL/min to achieve and maintain a postapplication mean arterial blood pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Primary endpoints were survival, survival time, post-treatment blood loss, and amount of resuscitation fluid. RESULTS: All animals treated with WS survived to 180 minutes and required only a single application. No animal in the AFB, QCG, or ACS group survived. One animal in the HC group survived. Survival (p < 0.05) and survival times (p < 0.0001) for WS animals were significantly greater than for all other groups. No significant difference in survival or survival time existed between the AFB, QCG, ACS, or HC groups. Post-treatment blood loss (p = 0.0099) and postresuscitation fluid volume (p = 0.006) was significantly less for animals treated with WS than for all other groups. No significant difference in these parameters existed between the AFB, QCG, ACS, and HC groups. CONCLUSION: WS was superior to the other hemostatic agents tested in this study of lethal arterial vascular injury. Additional study is warranted on this agent to determine its potential for use in combat and civilian trauma.

A new noninvasive method to determine central venous pressure.

UNLABELLED: Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. OBJECTIVES: We tested a noninvasive means of determining CVP (NICVP), by monitoring forearm volume changes in response to externally applied circumferential pressure to the upper arm veins. METHODS: Sixteen patients who were undergoing CVP monitoring as a part of their care had NICVP determined and compared with CVP. Volume changes were measured in the forearm with mercury-in-silastic strain gauge plethysmography. A pressure cuff is placed in the upper extremity. The cuff is inflated over 5s to a pressure above CVP but below diastolic arterial pressure (40 mmHg). This allows blood into the forearm but prevents venous return. After 45-60 s the cuff is rapidly deflated. NICVP was determined as the cuff pressure noted at the maximum derivative of the forearm volume decrease during deflation. NICVP was then compared to invasively measured CVP taken during the same period. RESULTS: A total of 48 trials (three per subject) were performed on 16 patients. The range of CVP recorded was 0-22 mmHg. The correlation between CVP and NICVP was 0.98 (95% CI: 0.95-0.98) (p<0.001). The bias between methods was 0.26 mmHg with the limits of agreement being 3.4 to -2.89 mmHg. When the average of three trials per patients was analysed the bias stayed at 0.26 mmHg but the limits of agreement improved to 2.54 and -2.03 mmHg. CONCLUSION: NICVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a valid tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.

Chronic implantation of transit-time flow probes on the ascending aorta of rodents.

This study describes the implantation of transit-time flow probes on the ascending aorta of rats while minimizing the risk of postoperative complications. Special emphasis is placed on our new method of rat intubation as well as the production of materials necessary for the implantation procedure such as endotracheal tubes and heparin bonded vessel catheters. The effects of these devices on the response to acute hypoxia were studied in rats following a 5-7 day recovery from the implantation procedure. Systemic and microvascular measurements were made on instrumented rats (n = 5) and non-instrumented controls (n = 3) that were ventilated with 21%, 15%, 10%, 8% and 5% oxygen. Arterial pressure, PO(2), lactate, and base deficit were not different between the implanted and control animals at any inspired oxygen concentration. Microvascular flow in the primary arterioles of the spinotrapezius muscle was also similar between the two groups at all inspired oxygen concentrations. We conclude that this novel methodology facilitates the measurement of whole body oxygen delivery in resting and haemodynamically-stressed rats.

Oxygenation monitoring of tissue vasculature by resonance Raman spectroscopy.

Resonance Raman spectroscopy offers a mechanism for the noninvasive measurement of in vivo and in situ hemoglobin oxygen saturation (HbO(2)Sat) in living tissue. Clinically informative signals can be provided by resonance enhancement with deep violet excitation. It is notable that fluorescence does not significantly degrade the quality of the signals. During the controlled hemorrhage and resuscitation of rats, signal intensity ratios of oxy- vs. deoxyhemoglobin from sublingual mucosa correlated with co-oximetry values of blood withdrawn from a central venous catheter. The spectroscopic application described here has potential as a noninvasive method for the diagnosis of clinical shock and guidance of its therapy.

Systemic responses to prolonged hemorrhagic hypotension.

Studies are needed to provide a rigorous examination of the relevance of monitored variables during prolonged hemorrhagic hypotension (HH). This study was designed to investigate the parameters that describe biochemical and O2 transport patterns in animals subjected to HH. Systemic parameters that could differentiate survivors from nonsurvivors were identified. An aortic flow probe was implanted in rats (n = 21) for continuous measurement of cardiac output. Experiments were performed 6-9 days after surgery. Rats were bled to a mean arterial pressure of 40 mmHg and kept at that level using Ringer-lactate solution. Arterial and venous blood pressures, gases, acid-base status, glucose, lactate, electrolytes, hemoglobin, O2 saturation, heart and respiratory rates, total peripheral resistance, and O2 delivery and consumption were measured before hemorrhage, soon after 40 mmHg was reached, and 0.5, 1, 2, 3, and 4 h later. Fifty-three percent of rats survived > or =3 h (survivors); others were considered nonsurvivors. Nonsurvivors showed a significantly greater degree of metabolic acidosis than survivors. Arterial PO2, respiratory rate, O2 saturation, O2 content, glucose, and pH were significantly higher in survivors. The rate of Ringer-lactate infusion, arterial K+, and PCO2 were lower in survivors. Arterial K+ and respiratory rate were the only parameters significantly different between survivors and nonsurvivors at all time points during HH. Arterial levels of K+ showed the clearest distinction between survivors and nonsurvivors and may explain the sudden death experienced by animals during HH. The data suggest that early respiratory and metabolic compensations are essential for survival of prolonged HH.

Continuous peripheral resistance measurement during hemorrhagic hypotension.

We tested the hypotheses that continuous total peripheral resistance (TPR) measurements are superior to intermittent data collection and that variables related to TPR can be used to distinguish between survivors and nonsurvivors (NS), respectively, of prolonged hemorrhagic hypotension (HH). One week after a transit-time ultrasound probe was implanted on their ascending aortas, 21 rats were subjected to 4 h of HH at 40 mmHg. Measurements were made before and up to 4 h after initiation of HH. Additional bleeding or Ringer L-lactate (RL) infusion was used to maintain HH. TPR was continuously measured online using recordings of blood flow and arterial pressure. Approximately 67% of the rats survived > or =3 h; others were considered NS. Data collected at 30-min intervals failed to detect the maximum value of TPR (TPRmax). The times to reach TPRmax were similar for survivors and NS and were strongly correlated with the bleeding end points and with the RL infusion-onset times. However, survivors showed higher TPRmax values than NS (P <0.005) and had a significantly longer period than NS during which TPR was above baseline level (116 +/- 20 vs. 51 +/- 10 min). In conclusion, 1) the transit-time ultrasound technique at high sampling rate allowed continuous and accurate real-time monitoring of TPR, 2) the bleeding end point and RL infusion-onset times may be used as surrogates of the time to TPRmax, 3) TPRmax of survivors and NS could be detected only using a continuous TPR measurement, and 4) differences between survivors and NS could be revealed by the continuous TPR curve.