Ultrasound-Guided Individualized Prophylactic Treatment Of Post-Spinal Hypotension During Cesarean Section

Objective:It is essential to maintain circulation stability in cesarean section to ensure mothers’and infants’safety.Spinal anesthesia is the standard method for elective cesarean section.Nevertheless,post-spinal hypotension（PSH）remains a common adverse event that may threaten mothers’and infants’safety.At present,the main prophylactic measures for PSH are vasopressors infusion and fluid supplementation.However,non-individualized vasopressors and fluid use may increase the adverse events,such as hypertension,bradycardia,tachycardia,arrhythmias,and even heart failure.We hope to use an individualized prophylactic strategy to reduce PSH incidence,minimize adverse reactions caused by overtreatment and increase circulation stability.However,no single predictor of PSH is used widely in clinical.As blood pressure generation depends on the three main factors:blood volume,cardiac output,and systemic vascular resistance,no single predictor was accurate enough for PSH prediction.Ultrasound is a convenient,rapid,and non-invasive method that can simultaneously measure blood volume,cardiac output and reflect cardiovascular tolerance under various positions.Thus,the purposes of the study are to review the predictors of PSH during the cesarean section,and try to find the valuable predictors;select ultrasound parameters based on the systematic review,and evaluate the advantage of multiple parameters’combination of ultrasound measurements in predicting PSH during cesarean section;guide the individualized prophylactic strategy of PSH based on the combined predictive parameters of ultrasound and prove its’efficacy on maternal circulation stability and fetus metabolism improvement.Methods:Part 1:Systematic review.Pub Med,Embase,Cochrane Library,Google Scholar,and Web of Science were searched for prospective observational studies,assessing the parameters’diagnostic accuracy for post-spinal hypotension in elective cesarean section up to September 20,2020.The searching strategy was to combine the following Medical Subject Headings and search terms:“spinal anesthesia/intrathecal anesthesia/combined spinal-epidural anesthesia,”“hypotension,”“predict/prediction/predictor/correlation,”“cesarean section/delivery.”We assessed the quality of studies with the QUADAS-2 tool.We classified and qualitatively analyzed the predictors and their predictive values involved in the review.Part 2:Prospectively observational study.Velocity-time integral（VTI）and left ventricular end-diastolic area（LVDEA）were measured by ultrasound in supine and left lateral positions before anesthesia.We calculated stroke volume and cardiac output based on these measurements.PSH was defined as a decrease of>20%from baseline mean arterial pressure between induction of spinal anesthesia and baby delivery.Patients were divided into hypotension group and normotension group according to their blood pressure.Binary linear logistic regression and ROC were used to analyze the parameters’predictive value for post-spinal hypotension.Part 3:Randomized controlled trial.All participants were assigned to standard prophylactic group（SP group）or individual prophylactic group（IP group）according to the random number generated by Excel 2010.In SP group,all patients received500ml voluven and 50ug.min^-1phenylephrine pumping from spinal injection to baby delivery.Patients in IP group received 500ml voluven if LVEDA_TS<11cm²and/or50ug.min^-1phenylephrine pumping if VTI%>1.3%or HR>87bpm from spinal injection to baby delivery.The following differences between the two groups were compared:the incidence and frequency of maternal circulatory adverse events（including hypotension,hypertension,bradycardia,and tachycardia）from spinal anesthesia to baby delivery,fetal umbilical cord blood gas analysis and Apgar score,maternal circulatory parameters,e.g.,cardiac output and the amount of phenylephrine and fluid.Results:Part 1:Thirty-six studies were included.We classified more than 30 predictors into seven groups according to their physiological implications and blood pressure effects.Maternal blood volume and fluid responsiveness,and postural pressure test had the highest probability of positive results.Six of the nine studies on maternal blood volume and fluid responsiveness could predict PSH effectively,of which VTI variation at different positions had the best predictive value（AUROC 0.8,95%CI[0.6-0.9]）.Four studies about supine stress test showed moderate predictive value of PSH（sensitivity 56%-78%,specificity 79%-91%）.Two studies showed that supine stress test combined with heart rate variability could enhance the latter’s predictive value.The predictive values were significant different in maternal baseline sympathetic-parasympathetic activity and peripheral perfusion.Maternal demographic characteristics and maternal baseline hemodynamics had the highest probability of negative resultsPart 2:Eighty-eight patients were enrolled,with 31 patients in normotension group and 57 patients in hypotension group.The top predictors were VTI%[AUROC 0.766（0.664-0.850）,P<0.001],supine LVEDA（LVDEA_s）[AUROC 0.711（0.605-0.803）,P=0.001],and heart rate[AUROC 0.707（0.600-0.799）,P=0.001].A combination of heart rate,LVDEA_s,and VTI%was significantly better at predicting hypotension than heart rate[AUROC 0.827 vs.0.707,P=0.020]or LVDEA_s[AUROC 0.827 vs.0.711,P=0.039]alone.The difference between this combination and VTI%was not significant[AUROC 0.827 vs.0.766,P=0.098].Part 3:One hundred and fifty-two patients were enrolled,with 77 patients in SP group and 75 patients in IP group.The number of patients without circulatory adverse events was no statistically significant difference between SP and IP groups[34（44.2%）vs.37（49.3%）,P=0.626].There were significantly more hypertension patients in SP group than in IP group（23（29.9%）vs.9（12%）,P=0.009）.SP group had a lower incidence of hypotension than IP group[11（14.3%）vs.21（28%）,P=0.047].The number of patients with bradycardia≥3 times was significantly higher in SP group than in IP group[9（11.7%）vs.2（2.7%）,P=0.032].The fetal umbilical artery（UA）PH（7.31[7.28-7.33]vs.7.32[7.30-7.36],P=0.038）and LAC（2.1[1.7-2.4]vs.1.9[1.7-2.1],P=0.002）,and umbilical vein（UV）of GLU（3.7[3.5-4.0]vs.3.4[3.2-3.8],P=0.033）were statistically significant between SP and IP group.All patients received phenylephrine pumping and voluven coloading in SP group;however,31（41.3%）patients avoid phenylephrine pumping and 31（41.3%）patients avoid voluven coloading in IP group,and the differences were significant.Conclusions:The systematic review suggested that it was challenging to predict PSH by one single predictor with sufficient accurate predictive value.Precise evaluation of blood volume and fluid responsiveness assessment may predict post-spinal hypotension with promising outcomes.Furthermore,the supine stress test may reflect the individual’s cardiovascular tolerance during hemodynamic fluctuations and optimize static state predictors’predictive value.The autonomic nervous system and peripheral perfusion index may predict post-spinal hypotension;however,influencing factors made the outcome unstable.The prospective observational study testified heart rate and LVDEA_swith VTI%could predict post-spinal hypotension in cesarean section more precisely than a single predictor.In the randomized controlled study,compared to standard prophylactic treatment,individual prophylactic interventions of PSH in the cesarean section based on the value of LVDEA_sand VTI%combined with HR could effectively prevent circulatory adverse events,including hypotension,hypertension,bradycardia,and tachycardia.The individualized prophylactic strategy reduced the incidence of hypertension,maintained a more stable heart rate,better guaranteed the placental perfusion and fetal metabolism and acid-base balance,and reduced the phenylephrine and voluven dosage significantly.