{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:25:31Z","timestamp":1788553531961,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Goal of Study: Spinal anesthesia for cesarean section is frequently associated with a high incidence of hypotension, which may bring about untoward effects for both the mother and fetus. Recently, norepinephrine has emerged as a promising alternative in maintaining blood pressure in the obstetric setting. Fluid administration is another technique still widely used to prevent maternal hypotension. The optimal fluid strategy to prevent maternal hypotension has not been elucidated yet. It has been recently suggested that the main strategy in the prevention and management of hypotension should be the combination of vasoconstrictive medications and fluid administration. The aim of this randomized study was to compare the incidence of maternal hypotension in parturients receiving either colloid preload or crystalloid co-load in the setting of prophylactic norepinephrine infusion during elective cesarean section under combined spinal\u2013epidural anesthesia. Materials and Methods: After ethics committee approval, 102 parturients with full-term singleton pregnancies were randomly allocated to either 6% hydroxyethyl starch 130\/0.4 5 mL\/kg before the onset of spinal anesthesia (colloid preload group) or Ringer\u2019s lactate solution 10 mL\/kg concurrent with the subarachnoid injection (crystalloid co-load group). In both groups, norepinephrine 4 \u03bcg\/min starting simultaneously with the administration of the subarachnoid solution was also administered. The primary outcome of the study was the incidence of maternal hypotension, defined as systolic arterial pressure (SAP) &lt;80% of baseline. The incidence of severe hypotension (SAP &lt; 80 mmHg), total dose of vasoconstrictive agents administered, as well as the acid\u2013base status and Apgar score of the neonate and any incidence of maternal side effects were also recorded. Results: Data analysis was performed on 100 parturients: 51 in the colloid preload group and 49 in the crystalloid co-load group. No significant differences were demonstrated between the colloid preload group and the crystalloid co-load group in the incidence of hypotension (13.7% vs. 16.3%, p = 0.933) or the incidence of severe hypotension (0% vs. 4%, p = 0.238). The median (range) ephedrine dose was 0 (0\u201315) mg in the colloid preload group and 0 (0\u201310) mg in the crystalloid co-load group (p = 0.807). The incidence of bradycardia, reactive hypertension, requirement for modification of vasopressor infusion, time to the first occurrence of hypotension, and maternal hemodynamics did not differ between the two groups. There were no significant differences in other maternal side effects or neonatal outcomes between groups. Conclusions: The incidence of hypotension with a norepinephrine preventive infusion is low and comparable with both colloid preload and crystalloid co-load. Both fluid-loading techniques are appropriate in women undergoing cesarean delivery. It appears that the optimal regimen for prevention of maternal hypotension is a combined strategy of a prophylactic vasopressor such as norepinephrine and fluids.<\/jats:p>","DOI":"10.3390\/jcm12041333","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T01:32:05Z","timestamp":1675819925000},"page":"1333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Colloid Preload versus Crystalloid Co-Load in the Setting of Norepinephrine Infusion during Cesarean Section: Time and Type of Administered Fluids Do Not Matter"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-4642","authenticated-orcid":false,"given":"Kassiani","family":"Theodoraki","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Hadzilia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Alexandra General Hospital of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Valsamidis","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Alexandra General Hospital of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-9939","authenticated-orcid":false,"given":"Konstantina","family":"Kalopita","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Alexandra General Hospital of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-9020","authenticated-orcid":false,"given":"Emmanouil","family":"Stamatakis","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Alexandra General Hospital of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","first-page":"CD004350","article-title":"Regional versus general anaesthesia for caesarean section","volume":"10","author":"Afolabi","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/ACO.0b013e32834588c5","article-title":"Maternal haemodynamic changes during spinal anaesthesia for caesarean section","volume":"24","author":"Dyer","year":"2011","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/ACO.0000000000000453","article-title":"The use of vasopressors during spinal anaesthesia for caesarean section","volume":"30","author":"Kee","year":"2017","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1213\/ANE.0b013e3181f2eae1","article-title":"The Dose-Dependent Effects of Phenylephrine for Elective Cesarean Delivery under Spinal Anesthesia","volume":"111","author":"Stewart","year":"2010","journal-title":"Anesth. Analg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1213\/ANE.0000000000003704","article-title":"Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial","volume":"129","author":"Sharkey","year":"2019","journal-title":"Anesth. Analg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ijsu.2020.10.006","article-title":"Prevention of hypotension during elective cesarean section with a fixed-rate norepinephrine infusion versus a fixed-rate phenylephrine infusion. A double-blinded randomized controlled trial","volume":"84","author":"Theodoraki","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14331","DOI":"10.1097\/MD.0000000000014331","article-title":"Efficacy and safety of norepinephrine versus phenylephrine for the management of maternal hypotension during cesarean delivery with spinal anesthesia: A systematic review and meta-analysis","volume":"98","author":"Xu","year":"2019","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1869189","DOI":"10.1155\/2018\/1869189","article-title":"The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia","volume":"2018","author":"Wang","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1213\/ANE.0000000000001239","article-title":"Should Norepinephrine, rather than Phenylephrine, Be Considered the Primary Vasopressor in Anesthetic Practice?","volume":"122","author":"Mets","year":"2016","journal-title":"Anesth. Analg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1097\/EJA.0000000000001371","article-title":"Fluid loading therapy to prevent spinal hypotension in women undergoing elective caesarean section: Network meta-analysis, trial sequential analysis and meta-regression","volume":"37","author":"Rijs","year":"2020","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/00000542-200510000-00012","article-title":"Prevention of Hypotension during Spinal Anesthesia for Cesarean Delivery: An effective technique using combination phenylephrine infusion and crystalloid cohydration","volume":"103","author":"Kee","year":"2005","journal-title":"Anesthesiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ijoa.2009.03.014","article-title":"A survey of the management of spinal-induced hypotension for scheduled cesarean delivery","volume":"18","author":"Allen","year":"2009","journal-title":"Int. J. Obstet. Anesthesia"},{"key":"ref_13","first-page":"CD002251","article-title":"Techniques for preventing hypotension during spinal anaesthesia for caesarean section","volume":"2020","author":"Chooi","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/anae.14841","article-title":"Prevention of hypotension after spinal anaesthesia for caesarean section: A systematic review and network meta-analysis of randomised controlled trials","volume":"75","author":"Fitzgerald","year":"2019","journal-title":"Anaesthesia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12630-009-9206-7","article-title":"Preload or coload for spinal anesthesia for elective Cesarean delivery: A meta-analysis","volume":"57","author":"Banerjee","year":"2010","journal-title":"Can. J. Anaesth."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3462529","DOI":"10.1155\/2017\/3462529","article-title":"Crystalloid Coload Reduced the Incidence of Hypotension in Spinal Anesthesia for Cesarean Delivery, When Compared to Crystalloid Preload: A Meta-Analysis","volume":"2017","author":"Ni","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_17","first-page":"UC01","article-title":"Fluid Administration Before Caesarean Delivery: Does Type and Timing Matter?","volume":"9","author":"Arora","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijoa.2014.06.006","article-title":"Comparison between colloid preload and crystalloid co-load in cesarean section under spinal anesthesia: A randomized controlled trial","volume":"23","author":"Tawfik","year":"2014","journal-title":"Int. J. Obstet. Anesthesia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"c869","DOI":"10.1136\/bmj.c869","article-title":"CONSORT 2010 Explanation and Elaboration: Updated guidelines for reporting parallel group randomised trials","volume":"340","author":"Moher","year":"2010","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/EJA.0000000000001152","article-title":"Norepinephrine for the prevention of spinal-induced hypotension during caesarean delivery under combined spinal\u2013epidural anaesthesia","volume":"37","author":"Wei","year":"2020","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"691809","DOI":"10.3389\/fphar.2021.691809","article-title":"The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension during Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1136\/bmj.300.6719.230","article-title":"Analysis of serial measurements in medical research","volume":"300","author":"Matthews","year":"1990","journal-title":"BMJ"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1097\/00000539-200104000-00036","article-title":"The Effects of an Increase of Central Blood Volume Before Spinal Anesthesia for Cesarean Delivery: A Qualitative Systematic Review","volume":"92","author":"Morgan","year":"2001","journal-title":"Anesth. Analg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103274","DOI":"10.1016\/j.ijoa.2022.103274","article-title":"The venous system during pregnancy. Part 2: Clinical implications","volume":"50","author":"Tsen","year":"2022","journal-title":"Int. J. Obstet. Anesthesia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1097\/ALN.0b013e31818a401f","article-title":"Continuous Invasive Blood Pressure and Cardiac Output Monitoring during Cesarean delivery: A randomized, double-blind comparison of low-dose versus high-dose spinal anesthesia with intravenous phenylephrine or placebo infusion","volume":"109","author":"Rosseland","year":"2008","journal-title":"Anesthesiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1016\/j.bja.2019.09.045","article-title":"Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: A Bayesian network meta-analysis of fetal and maternal outcomes","volume":"124","author":"Singh","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ijoa.2019.08.004","article-title":"Evaluation of the impact of enhanced recovery after surgery protocol implementation on maternal outcomes following elective cesarean delivery","volume":"43","author":"Kleiman","year":"2020","journal-title":"Int. J. Obstet. Anesthesia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/anae.14080","article-title":"International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia","volume":"73","author":"Kinsella","year":"2017","journal-title":"Anaesthesia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1213\/01.ane.0000437731.60260.ce","article-title":"A Randomized Controlled Trial of Variable Rate Phenylephrine Infusion with Rescue Phenylephrine Boluses versus Rescue Boluses Alone on Physician Interventions During Spinal Anesthesia for Elective Cesarean Delivery","volume":"118","author":"Taha","year":"2014","journal-title":"Anesth. Analg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1213\/ANE.0000000000002243","article-title":"Prophylactic Norepinephrine Infusion for Preventing Hypotension during Spinal Anesthesia for Cesarean Delivery","volume":"126","author":"Kee","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12871-019-0879-3","article-title":"Variable versus fixed-rate infusion of phenylephrine during cesarean delivery: A randomized controlled trial","volume":"19","author":"Hasanin","year":"2019","journal-title":"BMC Anesthesiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/ALN.0000000000002483","article-title":"Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension during Cesarean Delivery","volume":"130","author":"Hasanin","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1097\/00000542-199912000-00006","article-title":"Effects of Crystalloid and Colloid Preload on Blood Volume in the Parturient Undergoing Spinal Anesthesia for Elective Cesarean Section","volume":"91","author":"Ueyama","year":"1999","journal-title":"Anesthesiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/bja\/78.2.144","article-title":"Volume kinetics of Ringer\u2019s solution in female volunteers","volume":"78","author":"Hahn","year":"1997","journal-title":"Br. J. Anaesth."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/ACO.0b013e3283530dab","article-title":"Cesarean delivery fluid management","volume":"25","author":"Mercier","year":"2012","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1213\/ANE.0b013e31822c0f08","article-title":"Maternal Cardiac Output Changes After Crystalloid or Colloid Coload Following Spinal Anesthesia for Elective Cesarean Delivery: A randomized controlled trial","volume":"113","author":"McDonald","year":"2011","journal-title":"Anesth. Analg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1365-2044.1996.tb07698.x","article-title":"Effect of intravenous fluid preload on vasoactive peptide secretion during Caesarean section under spinal anaesthesia","volume":"51","author":"Pouta","year":"1996","journal-title":"Anaesthesia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1097\/00000542-199912000-00004","article-title":"Spinal Hypotension Associated with Cesarean Section: Will preload ever work?","volume":"91","author":"Rout","year":"1999","journal-title":"Anesthesiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R114","DOI":"10.1186\/cc9063","article-title":"Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury","volume":"14","author":"Silva","year":"2010","journal-title":"Crit. Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/bja\/87.3.406","article-title":"Volume kinetics of Ringer\u2019s solution during induction of spinal and general anaesthesia","volume":"87","author":"Ewaldsson","year":"2001","journal-title":"Br. J. Anaesth."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1213\/ANE.0b013e3182245af4","article-title":"Fluid Loading for Cesarean Delivery Under Spinal Anesthesia","volume":"113","author":"Mercier","year":"2011","journal-title":"Anesth. Analg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1213\/ANE.0b013e31826ac3db","article-title":"Phenylephrine Infusion versus Bolus Regimens During Cesarean Delivery Under Spinal Anesthesia: A double-blind randomized clinical trial to assess hemodynamic changes","volume":"115","author":"Doherty","year":"2012","journal-title":"Anesth. Analg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1001\/jama.2019.20833","article-title":"Effect of Hydroxyethyl Starch vs. Saline for Volume Replacement Therapy on Death or Postoperative Complications among High-Risk Patients Undergoing Major Abdominal Surgery: The FLASH Randomized Clinical Trial","volume":"323","author":"Futier","year":"2020","journal-title":"JAMA"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:16Z","timestamp":1760120836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041333"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041333","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}