This was a prospective, randomized, controlled study which enrolled shock patients in medical intensive care unit (MICU), neurology intensive care unit (NICU) and surgical intensive care unit (SICU) in West China Hospital from March 2017 to October 2017.
Patients were randomly assigned into the study group (CUOT group) and the control group (SC group). The patients assigned to the study group received shock treatment guided by PESCUS workflow(described in detail in the following part of method section), and patients in the control group received standard ICU care without the use of PESCUS workflow. The physicians (medical team) who participated in the study were those certified for critical care medicine and had over 5 years’ experience in critical care practice. Besides, they were also certified for bedside CCUS practice. The members of the CCUS team who assigned to perform the ultrasound examination according to the protocol were certified by the Chinese Critical Ultrasound Study Group (CCUSG) and had at least one-year practice experience. The measurements were recorded using the CX50 diagnostic ultrasound system (Philips, CX50, Bothell, WA, USA) and M-Turbo ultrasound system (FUJIFILM Sonosite, Bothell, WA, USA).
The protocol of the study was approved by the human ethics committees at Sichuan University (No. 2017(35)) and was carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association.
Patients admitted in MICU, SICU and NICU during the study period were screened for entry into this trial.
The study inclusion criteria are: (1) systolic blood pressure (SBP) < 90mmHg or mean blood pressure < 65mmHg or SBP decrease >40mmHg; (2) the onset of shock was less than 6 hours before ICU admission; (3) positive with at least one of the conditions below: Lactate level >2mmol/L; Capillary Refill Time >4.5s; Urine output per hour<0.5ml/kg; Clammy skin, limbs cold, unconsciousness. The patient who met all three above mentioned criteria was eligible for entry into the study. Patients were excluded from the study if they were: (1) age of <18 years; (2) pregnant; (3) refused to participate the study.
The patients were followed once enrolled and the data were recorded till death or end of ICU stay by dedicated investigators. Primary and secondary outcomes were analyzed after the trial was completed.
The study team discussed the trial’s risks, benefits and other aspects with the patients and, if required, the participants’ legal representatives, before the trial began. The study team gave the potential participant ample time and opportunity to ask questions about the trial and discuss it with relatives and family members. Informed written consent was obtained from a legal representative of the family under the circumstance that the patient was unconsciousness or sedated upon the enrollment. They were informed they have the right to withdraw consent at any time without penalty, repercussions or reason. In condition that the patient in salvage phase, the verbal consent was obtained immediately, and the informed written consent was signed after the rescue by the patient or the patient’s legal representative.
Once enrolled, patients in the study group were immediately screened by PESCUS workflow. The results of the CCUS exams were double checked by two different qualified CCUS team members and reported to the leading physician of the medical team right after the examination. Then, the PESCUS workflow based treatment in different shock phases were enforced by the medical team under the lead of the responsible physician. The protocol compliance was monitored consistently by a dedicated study coordinator, who also was responsible to provide timed prompts.
Patients in the control group received standard ICU care which including standard but not protocolized ultrasound exam if it was decided to be necessary by the team attending.
Pathophysiology and etiology treatment for shock based on critical ultrasonography(PESCUS) workflow
The PESCUS workflow was created by the Critical Care Medicine Department at West China Hospital based on the guidelines recommended shock diagnosis and treatment strategy (2, 25, 26) and the 3-year cumulative CCUS experience of the team. The protocol was not only an examination protocol to facilitate diagnosis but also to guide the treatment plan based on the established workflow (Figure 1).
If a patient was in shock salvage phase upon enrollment, a cardiorespiratory focused assessment performed by CCUS team will be initiated first (27), which included five standard views of heart (12) and ten views of lung. This bedside assessment was finished within 5 minutes and the results were then applied immediately to the patient to initiate “Pivotal treatment” or “Rapidly launching target treatment”, or both. The “Pivotal treatment” focused on finding whether there were ultrasonic signs of massive pulmonary embolism, cardiac tamponade and pneumothorax that could be the culprit to the life threatening shock, and the bedside interventions were then applied immediately to “salvage” the conditions such as guided thrombolysis, needle aspiration, and tube drainage. As those interventions were the key to save shock patients in such conditions, they were defined as “Pivotal treatment”. The “Rapidly launching target treatment” was then launched after “Pivotal treatment” or in the case patient did not require “Pivotal treatment” to shorten duration of salvage phase of shock, which included fluid challenge, inotrope and vasoactive drugs to treat the severe hypovolemia, pump failure and vasoparalysis, respectively.
For patients in optimization phase upon enrollment, hemodynamic detailed assessment with CCUS was performed. The examination which were performed within 20 minutes and the results were interpreted to guide treatment plan. The ECHO included the assessment of IVC, the right heart, the diastolic and systolic function of LV, the cardiac output, the left atrium pressure, and the deduced systemic resistance; the lung ultrasound included the eight-area exam focused on the lung water. The detailed ultrasonic assessment has two aims: the first is to diagnose the type of shock to guide etiological treatment, which has been shown leading to a better outcome in previous publications(28, 29), such as searching and treating massive hemorrhage in hypovolemic shock; screening infection sources for drainage or surgery in patients who have distributive shock pattern; and finding the regional wall motion abnormalities which may indicate acute coronary syndrome in patients undergoing cardiogenic shock. The second aim is to initiate goal directed titration therapy, which is through searching the abnormally pathophysiological changes of circulation to provide precise treatments (2,13,15,30) to improve the tissue perfusion. The treatments, such as fluid resuscitation and vasopressin administration, were titrated to an improvement of more than 10% lactate clearance every two hours (31,32). The medical team repeated the examination every four hours thereafter and adjusted the treatments accordingly until the end of the optimization phase, which is indicated by no increasing of the vasopressors, the lactate level reached less than 2.0 mmol/L or Capillary refill time <2s, and hour urine volume>0.5 ml/kg.h.(25,33,34).
The patients in de-escalation phase were performed with volume focused ultrasonic assessment which mainly focused on the IVC, the left atrium pressure and the lung water to evaluate whether there was fluid overload (35-37). If there were signs of fluid overload, diuresis was administrated without compromise the hemodynamics.
Details regarding the PESCUS workflow are provided in the Methods section in the Supplementary Appendix (S1).
Data were collected at baseline in both groups including age, sex, APACHE II, SOFA, diagnosis at admission, mean blood pressure, use of vasoactive agents, urine output per hour, lactate level, tidal volume and PEEP and PaO2/FiO2. Reports of CCUS exam, hemodynamics, fluid and drugs usage in both groups were recorded. The ICU mortality was our primary outcome. We also recorded the volume of fluid balance, source control, length of shock, duration of ventilation, length of ICU and hospitalization as secondary outcomes.
All analyses were conducted according to the intention-to-treat principle. The results were illustrated as continuous variables as means ±SD or medians and interquartile ranges depending on the normality of data. Categorical data were presented as proportions or percentages. Student’s t-test or the Wilcoxon rank-sum test was used to analyze differences between groups as needed. Fisher’s exact test was used to analyze categorical variables including the primary outcome. The Kaplan–Meier method was used to demonstrate patient risk of death from the start of the trial to the 28th day of treatment. The SPSS for mac (version 22.0; IBM Corp., Armonk, NY) was used for data statistical analysis. P < 0.05 was considered as statistically significant.