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Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
Correspondence to: S. Feng, Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu 610041, Sichuan Province, China.
Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
A systematic review of predictors of spinal anesthesia-induced hypotension.
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Blood volume/fluid responsiveness may predict spinal anesthesia-induced hypotension.
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Supine stress tests may optimize the predictive value of static state predictors.
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Autonomic nervous system and peripheral perfusion index were not reliable.
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Maternal demographics and baseline hemodynamic parameters were not useful.
Abstract
Background
Spinal anesthesia is the standard for elective cesarean section but spinal anesthesia-induced hypotension remains an important problem. Accurate prediction of hypotension could enhance clinical decision-making, alter management, and facilitate early intervention. We performed a systematic review of predictors of spinal anesthesia-induced hypotension and their predictive value during cesarean section.
Methods
PubMed, Embase, Cochrane Library, Google Scholar and Web of Science databases were searched for prospective observational studies assessing the diagnostic accuracy of predictors of spinal anesthesia-induced hypotension in elective cesarean section. The quality of studies was assessed and predictors were grouped in domains based on the type of predictor.
Results
Thirty-eight studies (n=3086 patients) were included. In most studies, patients received 500–1000 mL crystalloid preload or 500–2000 mL crystalloid coload. Vasopressors for post-spinal hypotension were boluses of ephedrine 5–15 mg and/or phenylephrine 25–100 µg in most studies. The hypotension rate varied from 29% to 80% based on the definition. For analysis, >30 predictors were classified into seven domains: demographic characteristics, baseline hemodynamic variables, baseline sympathovagal balance, postural stress testing, peripheral perfusion indices, blood volume and fluid responsiveness indices, and genetic polymorphism.
Conclusions
Environmental and individual factors increased outcome variability, which restricted the value of the autonomic nervous system and peripheral perfusion indices for prediction of spinal anesthesia-induced hypotension. Supine stress tests may reflect parturients’ cardiovascular tolerance during hemodynamic fluctuations and may optimize the predictive value of static state predictors. Future research for predicting spinal anesthesia-induced hypotension should focus on composite and dynamic parameters during the supine stress tests.
Hypotension causes problems for both the mother and fetus, including maternal nausea, vomiting, dizziness, rarely loss of consciousness, cardiac arrest, death; and fetal compromise.
Although various measures, such as intravenous fluid administration, prophylactic vasopressor administration, and patient positioning, are used to mitigate hypotension, it may not be avoided completely, with the incidence as high as 30% despite these measures.
Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: a randomised controlled trial.
Dose–response study of 4 weight-based phenylephrine infusion regimens for preventing hypotension during cesarean delivery under combined spinal-epidural anesthesia.
Hypotension occurs in ≥40% of patients after fluid loading, and adverse effects such as volume overload, anaphylaxis, and coagulopathy, although rare, must be considered.
Accurate prediction of spinal anesthesia-induced hypotension could enhance clinical decision-making, alter therapeutic management, and lead to appropriate early interventions. This study performed a systematic review with the aim of summarizing the possible predictors of spinal anesthesia-induced hypotension and their predictive value during cesarean section.
Methods
Search strategy
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA; Supplementary Material 1). Scientific databases, including PubMed, Embase, Cochrane Library, were searched for relevant publications using the following Medical Subject Headings and search terms: “cesarean section/delivery,” “hypotension,” “spinal anesthesia or intrathecal anesthesia or combined spinal-epidural anesthesia,” and “predict/prediction/predictor/correlation” (for a detailed search strategy see Supplementary Material 2). The initial search was conducted on August 15, 2020, restricted to English publications, and updated on December 19, 2020. Google Scholar and Web of Science database searches were additionally performed following the same strategy on December 19, 2020. All databases were searched since inception. Two investigators (FSM and YC) independently screened the databases using the described search strategy.
Study inclusion
The titles and abstracts of all articles retrieved were reviewed independently by FSM and YC, and disagreements were resolved by consensus. Full-text articles from potentially relevant abstracts were retrieved and assessed for eligibility. The bibliographies of all relevant articles were manually reviewed to identify additional articles. Studies were included if they fulfilled the following criteria: (1) prospective observational design, investigating parameters to predict spinal anesthesia-induced hypotension; (2) parturients of American Society of Anesthesiologists (ASA) Physical Status I-II undergoing elective cesarean section with spinal anesthesia or combined spinal-epidural anesthesia; (3) measurement of parameters before induction of spinal anesthesia; and (4) predictive data (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), odds ratio (OR), risk ratio (RR), area-under-the-receiver operating characteristic curve (AUROC), or correlation coefficient (r)) had been reported or could be calculated from the information provided. If raw data were not published but the study was otherwise eligible for inclusion, the authors were contacted to obtain additional information. Exclusion criteria were (1) parturients of ASA ≥III; (2) non-elective cesarean section; (3) epidural or general anesthesia; and (4) no available predictive data.
Data extraction
Two investigators (FSM and YC) independently abstracted data from all selected studies, with disagreement resolved by consensus. The following data were extracted from each study: (1) study characteristics (author, year, mode of anesthesia, intravenous fluid loading, and vasopressor use), (2) characteristics of trial participants (number of patients, definition of hypotension, hypotension rate), (3) parameters used to predict spinal anesthesia-induced hypotension, and (4) tested variables (cut-off threshold, sensitivity, specificity, PPV, NPV, OR, relative RR, AUROC, r).
Statistics
Extracted data from all included studies were entered into a spreadsheet. The quality of studies was assessed independently by two investigators (FSM and YC) using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2)
(Review Manager 5.3, clicktime.com, Inc., San Francisco, USA), and disagreements were resolved by consensus. The predictors identified were grouped into domains based on the type of predictor and analyzed qualitatively.
Results
Study flow
Initially, we identified 1046 studies of which 981 were excluded after title and abstract review. A full-text review of the 65 potentially eligible articles was performed, resulting in the exclusion of another 27 articles. Consequently, 38 studies were included in our analysis, including one randomized controlled trial with prospective data in one group (Fig. 1).
The characteristics of each individual study are presented in Table 1 and Supplementary Table 1. The quality of the studies is presented in Fig. 2. All studies were published between 1996 and 2020 (total n=3086). Patients in most studies received a 500 1000 mL crystalloid preload
as fluid infusion strategy. Vasopressors used to treat spinal anesthesia-induced hypotension were bolus doses of ephedrine 5–15 mg and/or phenylephrine 25–100 µg in most studies.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
Investigation of effect of blood pressure and heart rate changes in different positions (lying and sitting) on hypotension incidence rate after spinal anesthesia in patients undergoing caesarean section.
Bedside analysis of hear t rate variability by Analgesia Nociception Index (ANI) predicts hypotension after spinal anesthesia for elective Caesarean delivery.
Preoperative measurement of maternal abdominal circumference relates the initial sensory block level of spinal anesthesia for cesarean section: an observational study.
Investigation of effect of blood pressure and heart rate changes in different positions (lying and sitting) on hypotension incidence rate after spinal anesthesia in patients undergoing caesarean section.
Sympatho-vagal balance, as quantified by ANSindex, predicts post spinal hypotension and vasopressor requirement in parturients undergoing lower segmental cesarean section: a single blinded prospective observational study.
Maternal and anaesthesia related risk factors and incidence of spinal anaesthesia induced hypotension in elective caesarean section: a multinomial logistic regression.
The effects of uterine size with or without abdominal obesity on spinal block level and vasopressor requirement in elective cesarean section: a prospective observational study.
Correlation of symphysiofundal height and abdominal girth with the incidence of hypotension in cesarean section under spinal anesthesia using bupivacaine with fentanyl as adjuvant: a clinical study.
Observation of hemodynamic parameters using a non-invasive cardiac output monitor system to identify predictive indicators for post-spinal anesthesia hypotension in parturients undergoing cesarean section.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
Eighteen studies with 1805 patients reported the use of maternal demographic characteristics to predict hypotension (Supplementary Table 2). Among them, only three reported a weak relationship between maternal weight and body mass index (BMI) with spinal anesthesia-induced hypotension.
Observation of hemodynamic parameters using a non-invasive cardiac output monitor system to identify predictive indicators for post-spinal anesthesia hypotension in parturients undergoing cesarean section.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
reported that maternal weight gain during pregnancy was valuable in predicting spinal anesthesia-induced hypotension, however the sensitivity was low (53.1%). Fakherpour et al.
Maternal and anaesthesia related risk factors and incidence of spinal anaesthesia induced hypotension in elective caesarean section: a multinomial logistic regression.
Correlation of symphysiofundal height and abdominal girth with the incidence of hypotension in cesarean section under spinal anesthesia using bupivacaine with fentanyl as adjuvant: a clinical study.
found that the distance between the symphysis pubis and the fundus and abdominal girth could effectively predict spinal anesthesia-induced hypotension, however, this correlation was not confirmed by Kuok et al.
Preoperative measurement of maternal abdominal circumference relates the initial sensory block level of spinal anesthesia for cesarean section: an observational study.
The effects of uterine size with or without abdominal obesity on spinal block level and vasopressor requirement in elective cesarean section: a prospective observational study.
Fifteen studies with 1032 patients assessed the baseline maternal heart rate for prediction of spinal anesthesia-induced hypotension (Supplementary Table 3). Chamchad et al.,
reported the correlation coefficient (r) between baseline maternal heart rate and spinal anesthesia-induced hypotension was 0.35. Eleven other studies did not confirm this relationship.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
Maternal and anaesthesia related risk factors and incidence of spinal anaesthesia induced hypotension in elective caesarean section: a multinomial logistic regression.
reported a strong relationship between baseline systolic blood pressure (SBP) and spinal anesthesia-induced hypotension (relative RR 6.53). Two studies by Chamchad et al.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
Domain III. Baseline sympathovagal balance indices
Eight studies with 426 patients assessed the predictive value of maternal heart rate variability (HRV) (Supplementary Table 4). A variety of techniques are available for assessment, including three main methods: fast Fourier transformation (LF/HF),
initially proposed HRV as a predictive tool for spinal anesthesia-induced hypotension in 22 patients using point correlation dimension (PD2), reporting 100% accuracy. Fast Fourier transformation (LF/HF), a classic method of HRV analysis, was assessed in five studies. The LF/HF ratio was suggested as a predictor of hypotension by Hanss et al. (n=40)
Bedside analysis of hear t rate variability by Analgesia Nociception Index (ANI) predicts hypotension after spinal anesthesia for elective Caesarean delivery.
suggested that dynamic heart rate variations associated with different patient positions improved the predictive value compared with a static state.
Sympathovagal balance was analyzed in 416 patients in five studies using other techniques. Skin conductance monitoring is a noninvasive technology providing information about sympathetic tone by measuring sweat gland filling. Ledowski et al.
found no predictive value of skin conductance or anxiety score. The analysis of pulse rate variability (PRV) provides the assessment of autonomic nervous system (ANS) regulation of the heart as well as peripheral vascular regulation information. Bolea et al.
suggested that the pupil autonomic innervation may reflect the balance of sympathetic and parasympathetic systems and verified its predictive value for the onset of spinal anesthesia-induced hypotension. Kim et al.
used the deep breathing and hand grip tests (which may reflect parasympathetic and sympathetic functions) to predict spinal anesthesia-induced hypotension, finding an AUROC of approximately 0.6.
Investigation of effect of blood pressure and heart rate changes in different positions (lying and sitting) on hypotension incidence rate after spinal anesthesia in patients undergoing caesarean section.
with 181 patients confirmed that the supine stress test (SST) predicted severe systolic hypotension with a sensitivity of 55% to 80% and a specificity of 80% to 90%. In contrast, Frölich et al.
found that HR and BP variations during the orthostatic change were not good predictors of spinal anesthesia-induced hypotension (Supplementary Table 5).
Domain V. Peripheral perfusion indices
The perfusion index (PI) was investigated in seven studies with 549 patients, while one study with 41 patients assessed cerebral oxygen saturation (ScO2). Duggappa et al.
Domain VI. Blood volume and fluid responsiveness indices
Individuals who are hypovolemic before the initiation of spinal anesthesia may be at increased risk for spinal anesthesia-induced hypotension. Maternal blood volume and fluid responsiveness were evaluated in 11 studies with 658 patients (Supplementary Table 7). Kundra et al.
evaluated inferior vena cava collapsibility index (IVCCI) as a predictor of spinal anesthesia-induced hypotension; the AUROC was <0.5.
The pleth variability index (PVI) has predicted fluid responsiveness in mechanically ventilated patients with a high degree of sensitivity and specificity. However, the predictive value of PVI in two studies was moderate (AUROC 0.6 and 0.75) (Supplementary Table 7),
Observation of hemodynamic parameters using a non-invasive cardiac output monitor system to identify predictive indicators for post-spinal anesthesia hypotension in parturients undergoing cesarean section.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
reported the relationship between beta-2 adrenergic receptor (ADRB2) genetic polymorphism and blood pressure during spinal anesthesia-induced hypotension. Two copies of the ArgGln haplotype were associated with a lower risk for hypotension (52.2% vs 75.0%; OR 0.36, 95% confidence interval 0.15 to 0.91; P=0.042).
Discussion
Blood pressure depends on blood volume, cardiac output, and vascular resistance, which are modulated by the cardiovascular, ANS, and endocrine systems.
In theory, factors reflecting these three aspects could predict spinal anesthesia-induced hypotension. Many parameters for predicting hypotension during cesarean section with spinal anesthesia have been assessed. According to our review, accurate blood volume and fluid response assessments may predict spinal anesthesia-induced hypotension. Supine stress tests reflect cardiovascular tolerance during hemodynamic fluctuations and may optimize the predictive value of static state predictors. Environmental and individual factors increased outcome variability, thereby restricting the value of the ANS and peripheral PI for the prediction of spinal anesthesia-induced hypotension. Further study with larger sample sizes is necessary to confirm these findings.
Hypovolemia, resulting from decreased systemic vascular resistance after spinal anesthesia, is one possible reason for spinal anesthesia-induced hypotension. Pre-operative blood volume assessment was investigated in several studies as a predictor for spinal anesthesia-induced hypotension. Pleth variability index and IVCCI were the most studied, however findings were inconsistent. The PVI is a well-known predictor of fluid responsiveness in mechanically ventilated patients.
Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre.
However, in spontaneously breathing patients, fluid responsiveness assessment becomes problematic as the tidal volume and frequency of breathing vary among patients, and cardiopulmonary interactions are more complicated in such patients than in those on mechanical ventilation.
Respiratory variation in inferior vena cava diameter has limited ability to predict fluid responsiveness in other settings, particularly in spontaneously ventilated patients.
Furthermore, blood volume is not the only factor influencing blood pressure; this may explain why blood volume assessment for prediction of spinal anesthesia-induced hypotension is of limited value. Velocity time integral variation in different patient positions
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
have been used effectively to predict spinal anesthesia-induced hypotension. These two predictors were not only valuable for blood volume assessment but also may reflect myocardial contractility and carotid artery-corrected blood flow time may also reflect afterload. Thus, we believe that composite parameters reflecting preload, myocardial contractility and afterload are likely to be more useful for predicting spinal anesthesia-induced hypotension.
The SST may reflect different cardiovascular tolerances of individuals with aortocaval compression through changes in heart rate, blood pressure, or maternal discomfort. Kinsella et al.
demonstrated that women with reduced tolerance for the supine position were more likely to experience hypotension and had higher vasopressor requirements. However, Frölich et al.
found that heart rate and blood pressure changes between the lateral supine and upright positions were not predictive of hypotension, suggesting that the SST may be more suitable for pregnant individuals with different cardiovascular tolerance assessments of aortocaval compression. The combination of SSTs with other predictors, such as heart rate variability, may improve the predictive value of HRV assessment in the static state.
Bedside analysis of hear t rate variability by Analgesia Nociception Index (ANI) predicts hypotension after spinal anesthesia for elective Caesarean delivery.
Pre-operative ANS assessment, for example, by assessing HRV, may provide useful information regarding the risk for hypotension following induction of spinal anesthesia. However, sympathovagal balance is influenced by many factors, such as blood volume, anxiety,
A favorable environment for HRV assessment is quiet and temperature-controlled; furthermore, ensuring that the patient is calm is very important. In addition, the ANS may undergo rapid changes, so HRV assessment should be performed immediately prior to the induction of neuraxial anesthesia. Even with accurate assessment of ANS activity, the baroreceptor sensitivity of each patient may differentially affect cardiovascular adaptations.
Sympatho-vagal balance, as quantified by ANSindex, predicts post spinal hypotension and vasopressor requirement in parturients undergoing lower segmental cesarean section: a single blinded prospective observational study.
Furthermore, some predictors, such as skin conductance, detect peripheral ANS instead of central ANS activity and may be inaccurate or exhibit a time lag. Under ideal environmental and mental conditions, the baseline heart rate may also reflect cardiovascular sympathetic activity and a higher baseline heart rate indicate a higher risk of spinal anesthesia-induced hypotension.
The PI assesses peripheral perfusion dynamics due to changes in peripheral vascular tone. Even with a stable blood volume, the PI is commonly affected by other factors such as movement, temperature, psychological stress and anxiety, which induce sympathetic activation. It is difficult to control for these factors in awake patients, which may explain the inconsistent outcomes found.
Maternal demographics and baseline hemodynamic parameters to predict hypotension in this setting have been investigated but only a few demonstrated predictive value.
We speculate that these parameters are not direct determinants of blood pressure, restricting their predictive efficacy. Although polymorphisms within the ADRB2 gene were associated with increased risk,
genotype screening is not a routine procedure. Some studies addressed the predictive value of parameters measured after spinal anesthesia, for example, sensory block level,
These predictors were excluded from this systematic review because they do not help in the decision-making process for a prophylactic strategy against spinal anesthesia-induced hypotension.
Several limitations should be considered when assessing the clinical relevance of our results. Quantitative analysis was not performed because of obvious heterogeneity among studies. First, the doses of spinal drug(s), fluid loading and vasopressor use were very different among studies. Second, the definition of spinal anesthesia-induced hypotension and assessment of its predictors varied among studies. All these diverse study characteristics may influence the predictive value of the different parameters. Moreover, the predictive value of VTI variation or corrected blood flow time were only studied once and further investigation is needed. Finally, we did not include studies in which predictive data were not reported, those published in languages other than English, or studies which were unpublished, which may have increased the risk of reporting bias. However, to the best of our knowledge, this systematic review is the most comprehensive qualitative analysis of spinal anesthesia-induced hypotension predictors to date. Thus, this resource provides investigators in this area with a status report. Composite parameters reflecting preload, myocardial contractility and afterload may predict spinal anesthesia-induced hypotension, while the SST may be valuable for pregnant women with different cardiovascular tolerance assessments of aortocaval compression. To further examine these factors, future research should focus on composite and dynamic parameters during the SST.
In summary, an accurate evaluation of blood volume and fluid responsiveness assessment may predict post-spinal hypotension. Furthermore, the SST may reflect the individual’s cardiovascular tolerance during hemodynamic fluctuations and may optimize the predictive value of static state predictors. Environmental and individual factors increased outcome variability, thereby restricting the value of the ANS and peripheral PI for prediction of spinal anesthesia-induced hypotension.
Funding
This work was supported by a grant from the Science and Technology Department of Sichuan Province, China (No. 2018SZ0211).
Conflicts of interest
Author Zhimin Liao received research support from the Science and Technology Department of Sichuan Province, China (No. 2018SZ0211).
Appendix A. Supplementary data
The following are the Supplementary data to this article:
Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: a randomised controlled trial.
Dose–response study of 4 weight-based phenylephrine infusion regimens for preventing hypotension during cesarean delivery under combined spinal-epidural anesthesia.
Predictability of preoperative carotid artery-corrected flow time for hypotension after spinal anaesthesia in patients undergoing caesarean section: a prospective observational study.
Investigation of effect of blood pressure and heart rate changes in different positions (lying and sitting) on hypotension incidence rate after spinal anesthesia in patients undergoing caesarean section.
Observation of hemodynamic parameters using a non-invasive cardiac output monitor system to identify predictive indicators for post-spinal anesthesia hypotension in parturients undergoing cesarean section.
Maternal and anaesthesia related risk factors and incidence of spinal anaesthesia induced hypotension in elective caesarean section: a multinomial logistic regression.
Correlation of symphysiofundal height and abdominal girth with the incidence of hypotension in cesarean section under spinal anesthesia using bupivacaine with fentanyl as adjuvant: a clinical study.
Preoperative measurement of maternal abdominal circumference relates the initial sensory block level of spinal anesthesia for cesarean section: an observational study.
The effects of uterine size with or without abdominal obesity on spinal block level and vasopressor requirement in elective cesarean section: a prospective observational study.
Bedside analysis of hear t rate variability by Analgesia Nociception Index (ANI) predicts hypotension after spinal anesthesia for elective Caesarean delivery.
Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre.
Sympatho-vagal balance, as quantified by ANSindex, predicts post spinal hypotension and vasopressor requirement in parturients undergoing lower segmental cesarean section: a single blinded prospective observational study.
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