Yun-Te Chang

Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.

Objective: Epinephrine has been the primary drug for cardiopulmonary resuscitation (CPR) for more than a century. The therapeutic rationale was to restore threshold levels of myocardial and cerebral blood flows by its alpha1 (&agr;1) and alpha2 (&agr;2)-adrenergic agonist vasopressor actions. On the basis of coincidental observations on changes in microvascular flow in the cerebral cortex, we hypothesized that epinephrine selectively decreases microvascular flow. Design: Randomized prospective animal study. Setting: University-affiliated research laboratory. Subjects: Domestic pigs. Interventions: Four groups of five male domestic pigs weighing 40 ± 3 kg were investigated. After induction of anesthesia, endotracheal intubation was followed by mechanical ventilation. A frontoparietal bilateral craniotomy was created. Ventricular fibrillation was induced and untreated for 3 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections during CPR of 1) placebo, 2) epinephrine, 3) epinephrine in which both &agr;1- and beta (&bgr;)-adrenergic effects were blocked by previous administration of prazosin and propranolol, and 4) epinephrine in which both &agr;2- and &bgr;-adrenergic effects were blocked by previous administration of yohimbine and propranolol. Measurements and Main Results: Cerebral cortical microcirculatory blood flow (MBF) was measured with orthogonal polarization spectral imaging. Cerebral cortical carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were concurrently measured using miniature tissue optical sensors. Each animal was resuscitated. No differences in the number of electrical shocks for defibrillation or in the duration of CPR preceding return of spontaneous circulation were observed. Yet when epinephrine induced increases in arterial pressure, it significantly decreased Pbo2 tension and increased Pbco2 tension. Epinephrine therefore significantly decreased MBF and increased indicators of cerebral ischemia. Reduced MBF and magnified brain tissue ischemia during and after cardiopulmonary resuscitation were traced to the &agr;1-adrenergic agonist action of epinephrine. When the &agr;2 effects of epinephrine were blocked, reduced MBF and tissue ischemia persisted. No differences in cardiac output, end tidal Pco2, arterial Po2 and Pco2, and brain temperature were observed before inducing cardiac arrest and following return of spontaneous circulation. Conclusions: In this model, epinephrine through its &agr;1-agonist action had adverse effects on cerebral microvascular blood flow such as to increase the severity of cerebral ischemia during CPR.

Microcirculation during cardiac arrest and resuscitation

Objective:Direct observations of the microcirculation using orthogonal polarization spectral imaging have attracted attention and revealed that, especially in cardiogenic and distributive shock, there is discordance between the macrocirculation and the microcirculation. We evaluated serial changes and the effects of epinephrine on microcirculatory blood flow in the most severe form of circulatory failure, namely, cardiac arrest. Design and Setting:Controlled laboratory animal study. Subjects and Interventions:A total of 15 pigs were subjected to 5 mins of ventricular fibrillation and 5 mins of precordial compression before electrical defibrillation was attempted. In a subset, six animals received 1 mg of epinephrine after 1 min of precordial compression. Measurements and Main Results:Microcirculatory blood flow was visualized in the sublingual mucosa at baseline and 0.5, 1, and 5 mins of ventricular fibrillation, at 1 and 5 mins of precordial compression, and at 1 and 5 mins after return of spontaneous circulation. In addition, coronary perfusion pressure was recorded. Microcirculatory blood flow decreased dramatically in the 0.5 min after the onset of ventricular fibrillation. Precordial compression partially restored microcirculatory blood flow in each animal but to a significantly greater extent in animals that achieved return of spontaneous circulation. These changes were paralleled by similar changes in coronary perfusion pressure. Both variables were highly correlated. Administration of epinephrine resulted in a massive reduction of microcirculatory blood flow that lasted for ≥5 mins. Conclusions:In this model, microcirculatory blood flow was highly correlated with macrocirculatory hemodynamics, including coronary perfusion pressure in distinction with septic shock. Administration of epinephrine dramatically decreased microcirculatory blood flow.

One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest

Background— The success of resuscitation with a 1-shock versus the conventional 3-shock defibrillation protocol was investigated subject to the range of treatment variation imposed by automated external defibrillators (AEDs). Methods and Results— Ventricular fibrillation was induced in 44 domestic pigs. After 7 minutes of untreated VF, animals were randomized among 4 groups representing all combinations of the 1- versus 3-shock protocol and 2 different AED regimens (AED1, AED2). Because few AEDs support a 1-shock protocol, manual defibrillators were used to replicate the AED treatment regimen: electrical waveform, dose sequence, and cardiopulmonary resuscitation (CPR) interruption intervals. Initial shock(s) were delivered, followed by 60 seconds of CPR, and the treatment was repeated until resuscitation was successful or for 15 minutes. The 1-shock protocol was associated with improved outcome, reducing CPR interruptions from 45% to 34% of total resuscitation time (P=0.019) and increasing survival from 64% to 100% (P=0.004). Survival was 91% for AED1 versus 36% for AED2 (P=0.024) with a 3-shock protocol but was increased to 100% for both by adoption of a 1-shock protocol. Improvements in postresuscitation left ventricular ejection fraction and stroke volume were observed with AED1 compared with AED2 (difference of means, 15% and 28% of baseline respectively, P<0.001) regardless of defibrillation protocol. Conclusions— Adoption of a 1-shock versus a 3-shock resuscitation protocol improved survival and minimized outcome differences imposed by variations in AED design and implementation. When a conventional 3-shock defibrillation protocol was used, however, the choice of AED had a significant impact on resuscitation outcome.

Comparison of buccal microcirculation between septic and hemorrhagic shock.

Objective:Microcirculatory perfusion is disturbed in sepsis, and global hemodynamics does not necessarily reflect microcirculatory blood flow. In this study, we investigated the effect of the same level of mean arterial pressure (MAP) or cardiac index on the changes in buccal microcirculation between septic and hemorrhagic shock. Design:Prospective, controlled laboratory study. Setting:University-affiliated research laboratory. Interventions:A total of 20 Sprague-Dawley rats were divided into four groups: 1) septic shock induced by cecal ligation and perforation: when MAP decreased to 80 mm Hg, saline was infused at a rate of 25 mL·kg−1·hr−1 for 2 hrs; 2) both time- and MAP-matched hemorrhagic shock: ∼30% of total blood volume was withdrawn during the corresponding interval, followed by infusion aiming to restore MAP as required when MAP decreased to 80 mm Hg; 3) both time- and cardiac index–matched hemorrhagic shock: ∼40% of total blood volume was withdrawn during the corresponding interval until MAP decreased to 50 mm Hg, which generally generated a cardiac index similar to those in septic animals, followed by infusion at the same rate for 2 hrs; and 4) sham control: animals underwent the same procedure except no cecal ligation and perforation, bleeding, and infusion. Measurements and Main Results:Buccal microcirculation was visualized with the aid of an orthogonal polarization spectral image device. A semiquantitative score was calculated for vessels of <20 &mgr;m, primarily representing the capillaries. Impaired buccal capillary blood flows in septic animals were more severe than those in MAP-matched hemorrhagic animals and were similar to those in cardiac index–matched hemorrhagic animals during the hypoperfusion period before infusion. Significantly improved global hemodynamics after resuscitation cannot effectively improve the buccal capillary blood flows in septic animals, in contrast to those in MAP-matched and cardiac index–matched hemorrhagic animals. Conclusions:Impaired microcirculatory alteration in septic shock is more severe than hemorrhagic shock; microcirculation is relatively independent of improved systemic hemodynamics, in contrast to those in hemorrhagic shock.

Comparison of rectilinear biphasic waveform with biphasic truncated exponential waveform in a pediatric defibrillation model.

Objective:To compare the rectilinear biphasic waveform with a biphasic truncated exponential waveform for pediatric defibrillation. Design:Prospective, randomized study. Setting:Experimental laboratory of a university-affiliated research institute. Subjects:Male domestic piglets (4–24 kg). Interventions:Eleven piglets (4–8 kg), which represented a patient <1 yr old, and ten piglets (16–24 kg), which represented a pediatric patient between the ages of 2 and 8 yrs, were anesthetized, intubated, and mechanically ventilated. Ventricular fibrillation was induced and maintained for 30 secs, and a predetermined shock was then delivered to defibrillate. Following defibrillation, the animal was permitted to stabilize hemodynamically for 4 mins. Fifty shocks were applied to each animal using a randomization schedule based on a predetermined permutation of 50. The 50 shocks were 25 shocks for each rectilinear biphasic and biphasic truncated exponential waveforms, comprising five shocks at five energy settings. Each group of five shocks was fixed at a predetermined energy value, depending on the body weight of the animal. Dose-response curves were constructed using logistic regression. Aortic pressure, electrocardiogram, left ventricular pressure, and left ventricular pressure value of 40 mm Hg were continually measured. Measurements and Main Results:Dose-response curves determined defibrillation thresholds at 50% (D50) and 90% (D90) probability of success. The rectilinear biphasic waveform defibrillated with <90% of the D50 and D90 energies required for a biphasic truncated exponential waveform. The rectilinear biphasic waveform also successfully defibrillated with significantly less energy per body weight and per heart weight compared with a biphasic truncated exponential waveform. Conclusions:The rectilinear biphasic waveform has superior defibrillation performance compared with a biphasic truncated exponential waveform in a piglet defibrillation model for young children.

Effects of biphasic waveforms on outcomes of cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest.

Objectives:The effects of two clinically available biphasic waveforms on the success of defibrillation and postresuscitation myocardial dysfunction after prolonged ventricular fibrillation were compared with two newly designed dual-path sequential and simultaneous rectilinear biphasic waveforms. Defibrillation via sequential pulses and encircling, overlapping multiple pathway may depolarize a larger myocardial mass and facilitate transthoracic defibrillation. Design:Animal study. Setting:Experimental laboratory. Subjects:Thirty-two 40 ± 3 kg pigs. Interventions:Ventricular fibrillation was ischemically induced in 32 pigs. After 7 mins of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated and continued for 5 mins. Animals were then randomized to receive up to three shocks with a) single-path rectilinear biphasic waveform; b) single-path biphasic truncated exponential waveform; c) dual-path rectilinear biphasic sequential defibrillation; or d) dual-path rectilinear biphasic simultaneous defibrillation. Measurements and Main Results:Rectilinear biphasic, dual-path sequential defibrillation, and simultaneous defibrillation had significantly fewer shocks (1.1 ± 0.4, 1.4 ± 0.5, 1.3 ± 0.7, respectively) before restoration of spontaneous circulation than biphasic truncated exponential waveform (2.6 ± 1.4, p < .005) and less postresuscitation myocardial dysfunction (p < .05). Also, dual-path sequential defibrillation had higher postresuscitation ejection fraction than rectilinear biphasic and dual-path simultaneous defibrillation (p < .005). Conclusions:The energy requirements for terminating ischemically induced ventricular fibrillation were significantly lower and minimized early postresuscitation myocardial dysfunction in the rectilinear biphasic, dual-path sequential defibrillation, and simultaneous defibrillation than the biphasic truncated exponential waveform. Dual-path sequential defibrillation had less postresuscitation myocardial dysfunction than rectilinear biphasic and dual-path simultaneous defibrillation, but at 72 hrs these differences were no longer significant.

Microcirculation During Low Flow States

Microcirculation represents the ultimate determinant of the outcomes of circulatory shock states. Microcirculatory function is the prerequisite for adequate tissue oxygenation and therefore organ function. It transports oxygen and nutrients to tissue cells, ensures adequate immunological function, and, during disease, delivers therapeutic drugs to target cells. It consists of the smallest blood vessels: arterioles, capillaries and venules [1] (Fig. 1). Previous techniques for studying microcirculation (microscopes, laser Doppler and plethysmography) were able to provide only global measurements of microvascular blood flow, expressed as average values of the diameter or direction of a single vessel. Recent technological developments using orthogonal polarisation spectral (OPS) imaging techniques allow the direct visualisation and monitoring of microcirculation at the bedside [2], [3] (Fig. 2). The OPS imaging technology is a non-invasive method for directly visualising multiple conditions of the microcirculation that have clinical applications for humans. It allows the quantitative measurement of the diameter of vessels, the velocity of red blood cells and functional capillary density [4]. The technique uses a linearly polarised light to illuminate the area of interest. The light is reflected from the tissue source and forms an image of the illuminated region within the target of the video camera. The image is then captured through a polariser, which is oriented orthogonally to the plane of the illuminating light [5].

The Effects of Gasping During Cardiac Arrest and Cardiopulmonary Resuscitation

Gasping, observed commonly at the beginning and at the end of life [1]–[5], is a striking phenomenon characterised by fast and forceful inspirations. Gasping is especially prominent in the human newborn. In 1812, Legallois [6] described gasping in a variety of animal species and also in human patients. The Glossary Committee of the International Union of Physiologic Sciences defined a gasp as ‘an abrupt, sudden transient inspiratory effort’ [7].