Since the inception of modern cardiopulmonary resuscitation in the late 1950s, half a century of medical practice and theoretical discussions have led to encouraging achievements. After cardiac arrest by cardiopulmonary resuscitation (CPR) about 30-40% of the recovery of autonomic circulation (ROSC), however, due to cardiac arrest and resulting in prolonged systemic complete ischemia, the body enters a more complex new pathophysiological process after ROSC, mainly including: brain damage after cardiac arrest, myocardial damage after cardiac arrest, systemic ischemia/reperfusion injury, causing or contributing to cardiac The new pathophysiological processes include brain damage after cardiac arrest, myocardial damage after cardiac arrest, systemic ischemia/reperfusion injury, and various pre-existing conditions (or causes) that caused or contributed to cardiac arrest/have not been eliminated.
The severity and clinical manifestations of the pathophysiologic abnormalities of PRS are inconsistent, depending on the duration of cardiac arrest, the duration of CPR, and the underlying medical condition. However, the concept of “resuscitation” is nowadays widely used, such as fluid resuscitation in severe sepsis and various shock resuscitations, which do not have
In addition, literally speaking, “post-resuscitation” seems to imply the end of the resuscitation process, while in fact, as mentioned above, after cardiac arrest by CPR and ROSC, the body enters a new pathophysiological process that requires further resuscitation. Therefore, a new academic consensus was formed by representative experts from several international related societies to name the abnormal pathophysiological state after cardiac arrest ROSC as post-cardiac arrest syndrome.
1. The main pathophysiological changes of PCAS
(1) Brain damage after cardiac arrest: It is a common cause of death and neurological disability in patients. The brain tissue is poorly tolerant to hypoxia, and the cerebral blood flow stops suddenly (clinically) in 15 seconds; brainstem function stops in 1 minute (end-stage respiration, pupil fixation); anaerobic metabolism stops in 2-4 minutes, and ATP is no longer produced; ATP is consumed in 4-6 minutes, and all energy-demanding reactions (sodium pump, metabolism, vital activities) stop, and the damage is irreversible. In prolonged cardiac arrest after ROSC, even if high perfusion pressure is provided, on the one hand, the increase in cerebral perfusion pressure and the impairment of cerebrovascular self-regulation usually cause reperfusion congestion in the brain, resulting in cerebral edema and reperfusion injury; on the other hand, cerebral microcirculatory impairment is still seen, resulting in persistent ischemia and focal infarction of brain tissue. The brain damage after cardiac arrest is characterized by coma, convulsions, myoclonus, cognitive impairment, stroke, vegetative state, and brain death. The mechanisms involved are complex, including neuronal excitotoxicity, calcium imbalance, free radical formation, pathological protease cascade reactions, and activation of cell death signaling pathways.
(2) Myocardial damage after cardiac arrest: cardiac arrest victims are in a hemodynamic instability after ROSC, manifested by reduced cardiac output, hypotension, and arrhythmias; the mechanisms include myocardial insufficiency, reduced intravascular volume, and derangement of vascular self-regulation. It should be recognized that myocardial dysfunction after ROSC in cardiac arrest is mainly due to diffuse myocardial hypokinesis (myocardial stuttering), which is reversible and treatable.
(3) Systemic ischemia/reperfusion injury: cardiopulmonary resuscitation or chest compressions can only partially solve the problem of oxygen and nutrient delivery and expulsion, and insufficient tissue oxygen supply persists even after ROSC due to myocardial insufficiency, hemodynamic instability and microcirculatory disorders. And reperfusion and reoxygenation inevitably lead to reperfusion injury. Systemic ischemia and reperfusion cause extensive immune system and coagulation system activation, which in turn produce systemic inflammatory response syndrome, hypercoagulable state, suppressed adrenal function, impaired tissue oxygen supply/oxygen demand, increased susceptibility to infection, acid-base imbalance and water-electrolyte disturbance, stress ulcers and intestinal bleeding, hyperglycemia, and multi-organ failure, which have similarities with severe sepsis.
(4) Various pre-existing conditions (or causes) that cause or contribute to cardiac arrest and have not been eliminated, such as acute coronary syndrome, pulmonary disease, sepsis, hemorrhage, and various toxicities (toxic or drug overdose). The diagnosis and treatment after cardiac arrest is even more difficult because of the complexity of the pre-existing conditions themselves.
2.Resuscitation from cardiac arrest
The high mortality rate of ROSC patients is related to their unique pathophysiological characteristics. Among the 30-40% of patients with ROSC mentioned above, only about 10% eventually survive and are discharged from the hospital. According to the analysis, the causes of death after ROSC are approximately 50% cardiac, 30% cerebral and 20% other. The high mortality rate of ROSC patients after resuscitation from cardiac arrest is associated with their specific pathophysiological features. First, unlike tissue ischemic injury due to focal vascular lesions, systemic tissue hypoxic injury due to cardiac arrest is not compensated for each other; the death of half of the cells of the tissue means that tissue function is irreversible and irreplaceable for many physiological functions. Secondly, ROSC is not the same as recovery of the great circulation; ROSC is only the recovery of the voluntary heartbeat, whereas the recovery of the great circulation implies some balance or stability of the effective hemodynamic state, i.e., the interaction between cardiac output (CO), peripheral vascular resistance (TPR), and blood pressure (BP). Resuscitation of the third major circulation is not equivalent to restoration of microcirculation. Even if the autonomic circulation is completely restored to normal, the full recovery of cerebral circulation will take about 6-12 hours depending on the time and condition of disconnection. Fourth, microcirculatory perfusion is followed by injury ~~ reperfusion injury. Reperfusion injury may involve a variety of mechanisms such as inflammatory factor injury, calcium overload injury, etc., but the causal relationship between the mediators is not yet clear, and it is not known how to antagonize, but no perfusion is bound to lead to death.
3.Processing of PCAS
If ROSC can be achieved soon after cardiac arrest, then PCAS will not occur. Not surprisingly, the management of PCAS emphasizes its timeliness, with a particular focus on the role of time in the treatment strategy: early restoration of autonomic circulation and tissue microcirculation; antagonism of reperfusion injury; and reduction of tissue metabolism.
(1) The main monitoring components include general monitoring, hemodynamic monitoring, and brain monitoring.
(2) General monitoring: vital signs, urine output, pulse oxygen saturation, continuous ECG monitoring, CVP, ScvO2, arterial blood gases, serum lactate, electrolytes, routine blood count, chest X-ray; 3.1.2 Hemodynamic monitoring: echocardiography, cardiac output (non-invasive or invasive monitoring)
(3) Brain monitoring: EEG, CT, MRI. 3.2 Early hemodynamic treatment goals: early hemodynamic optimization, i.e., targeted therapy, is a major approach to restore and maintain the balance between systemic oxygen delivery and demand, given that the underlying pathophysiological state of PCAS – systemic ischemia and reperfusion injury, etc. – is similar to that of severe sepsis, hemodynamic optimization should, in theory, also improve the regression after cardiac arrest; at the same time, toxicity is not identical. Based on available studies and experience, the key to successful early hemodynamic optimization is the early initiation of comprehensive monitoring and aggressive interventions to achieve goals in preload, myocardial contractility, arterial oxygen content, and systemic oxygen utilization within hours of abnormalities through fluid therapy, cardiopulmonary and vasopressor drugs, and appropriate oxygen therapy. However, there are no randomized prospective clinical studies to clarify the early hemodynamic goals after cardiac arrest, and the limited data available suggest that restoration or maintenance of central venous pressure at 8-12 mmHg, mean arterial pressure at 65-100 mmHg, central venous oxygen saturation at 70% or less, and urine output at 1.0 mL/kg-1/h~1 are appropriate. In addition, blood lactate concentrations are high in the early post-ROSC period, and detection of lactate clearance is a good indicator of hemodynamic optimization. The target hemoglobin concentration has not been determined (one study on PCAS hemoglobin concentration reported a target value of 9 to 10 g/dL).
Oxygenation and Mechanical Ventilation.
Oxygen concentration during CPR is 100% (FiO2=1.0), and clinicians also usually continue to give the patient ROSC after
a period of pure oxygen; however, there is growing clinical evidence that excess oxygen is detrimental to postischemic neurons in the early stages of tissue reperfusion; reducing the inspired oxygen concentration immediately after ROSC to exactly maintain arterial oxygen saturation in the 94% to 96% range is desirable to reduce adverse neurological outcomes.
It has been shown that hyperventilation can aggravate ischemic damage to the brain by constricting cerebral arteries and can increase intrathoracic pressure and decrease cardiac output; hyperventilation (using a low tidal volume pulmonary protection strategy) can lead to hypoxemia and hypercapnia, which can also be harmful to post-resuscitation patients by increasing intracranial pressure and producing mixed acidosis (which is common after ROSC). Unfortunately, there is no evidence to date to support a specific tidal volume after cardiac arrest, but in general, a tidal volume of ≥6 ml/kg may be required, and adjustment to maintain a normal PaCO2 level based on arterial blood gas analysis would be most reasonable. Mixed venous oxygen saturation (SVO2) is an important indicator of the balance of tissue oxygen supply and demand, and the placement of a floating catheter to monitor SVO2 during early resuscitation is not widely used in clinical practice. Studies have confirmed that central venous oxygen saturation (SCVO2) and SVO2 are very close (SCVO2 values are 10% higher than SVO2 values) and have the same value in reflecting the balance of tissue oxygen supply and demand, and SCVO2 monitoring is more clinically feasible.
Circulatory support.
PCAS manifests as a state of hemodynamic instability, such as arrhythmias, hypotension, and low cardiac output. The cardiac approach includes maintenance of electrolyte levels, electroshock diversion and pharmacotherapy; an effective intervention for hypotension is intravenous rehydration to improve right ventricular filling pressures, and studies have shown that PCAS patients rehydrated up to 3.5±1.6 L of crystalloid in the first 24 h, resulting in a CVP of 8-12 mm Hg. CVP is an indirect indicator of volume status, i.e., preload, through pressure, and is susceptible to multiple factors such as cardiac and vascular It is susceptible to multiple factors such as cardiac and vascular compliance, thoracic pressure (PEEP above 10 mmHg increases CVP significantly), valvular regurgitation, significant abdominal distension or intestinal obstruction, etc. (especially significant when intra-abdominal pressure reaches 20 mmHg or more), and should therefore be considered in a comprehensive manner when evaluating its clinical significance. It should also be noted that some disease states can not only be the cause of cardiac arrest, but also directly affect preload themselves such as pulmonary thromboembolism, pneumothorax (especially tension), right ventricular infarction, and pericardial tamponade. If these hemodynamic goals are not achieved despite adequate volume replacement, cardiac and vasoactive agents should be used; in general, extensive myocardial insufficiency after cardiac arrest is reversible and responds well to cardiac drugs, but the severity and duration of myocardial insufficiency largely affects patient survival. To date, there are no reports on which cardiopulmonary and vasopressor drugs are more effective alone or in combination. In cases where volume replacement and the use of vasoactive and cardiopulmonary drugs have failed to restore tissue perfusion, the use of mechanical circulatory aids such as intra-aortic balloon counterpulsation should be considered, as the latter may provide good circulatory support.
Management of ACS.
Coronary angiography should be performed immediately in patients with ST-segment elevation myocardial infarction causing PCAS, and PCI can be done if indicated, or thrombolytic therapy can be considered if PCI is not possible. Induced hypothermia can be induced by intravenous “cold” fluids (saline or Ringer’s solution, 30 ml/kg) or by traditional inguinal, axillary, or cephalic placement. The use of sedatives or neuromuscular blocking agents to counteract the chills can be done by placing ice packs in the groin, axilla and head and neck. The use of an external hypothermia device (water or air circulating hypothermic blanket or pad) or an internal hypothermia device (femoral or subclavian vein hypothermic infusion catheter) is an effective way to maintain hypothermia in a specific range (to avoid significant fluctuations in body temperature). The rate of rewarming is not yet determined, but the current consensus is 0.25-0.5°C/h. During the course of treatment, extra attention should be paid to both the induction and rewarming phases, as rapid changes in metabolic rate, plasma electrolyte concentration and hemodynamic status may occur. The fever in the first 72h should be treated with antipyretics, while attention should be paid to seizure control and prevention.
Acidosis.
During CPR, despite effective chest compressions, cardiac output decreases significantly (the best closed CPR produces 20-30% of normal CO), tissue hypoxia, enhanced anaerobic cellular enzymes, increased lactate production, and more severe tissue and cellular acidosis occur, but because of the lack of strong evidence that sodium bicarbonate is effective during CPR, it is generally not routinely applied. However, if alveolar ventilation is adequate and metabolic acidosis is not completely corrected, a small amount of sodium bicarbonate may be applied, generally to achieve a CO2 binding capacity of 20 mmol/L and a pH of 7.2. It should also be noted that serum HCO3- and pH values are constantly changing dynamically during CPR, and it takes some time for HCO3~ to reach intra- and extracellular equilibrium, so measurements at one point in time can hardly reflect the actual changing situation of the body. In addition, recent studies have shown that the blood glucose concentration of PCAS patients should preferably be controlled below 8 mmol/L, but below 6.1 mmol/L does not help to reduce mortality, but rather risks hypoglycemia. There is no sufficient evidence that the use of any neuroprotective drugs can reduce brain injury in patients with PCAS, and there is no effective evidence to confirm that glucocorticoids improve the long-term prognosis of PCAS. Pneumonia in patients due to aspiration or mechanical ventilation is probably the most important complication in comatose patients with PCAS, and the risk of pneumonia in the 1st 48 h of PCAS is significantly increased compared with other intubated patients. Other issues related to nutritional and metabolic support, protection of gastrointestinal function, and management of various pre-existing conditions that cause or contribute to cardiac arrest are not addressed here.