Why was this consensus statement developed? Advances in clinical practice are sometimes inhibited by a multitude of different options that need to be selected. There has been significant variation in the treatment of spinal anaesthesia-induced hypotension. These guidelines are designed to provide clinicians with specific best-practice plans that will cover a wide range of drug and equipment availability. Detailed recommendations are provided for the management of hypotension in resource-rich and resource-poor environments. How does this consensus statement differ from other available guidelines? The American Society of Anesthesiologists/Society for Obstetric Anesthesia and Perinatology Task Force, and the UK National Institute for Health and Care Excellence, have made generic recommendations on this topic 1, 2. We are unaware of detailed guidelines from any organisations. We aim to offer independent, pragmatic advice that will be of benefit to clinicians and the women we treat. Hypotension is a very common consequence of the sympathetic vasomotor block caused by spinal anaesthesia for caesarean section. Maternal symptoms such as nausea, vomiting and dyspnoea frequently accompany severe hypotension, and adverse effects on the fetus, including depressed Apgar scores and umbilical acidosis, have been correlated with severity and duration of hypotension. Ephedrine, a mixed α- and β-adrenergic agonist, became the drug of choice in obstetric anaesthesia following work that found that it was the best vasopressor for preservation of uterine blood flow in a sheep model of drug-induced hypertension. However, higher doses of ephedrine, used clinically in attempts to reduce hypotension, were found not to improve neonatal acidosis, but rather the reverse 3; this is now acknowledged to be because ephedrine has a direct effect on fetal metabolism that negates any improvement in uterine blood flow produced by normalising blood pressure 4, 5. Clinical work dating from the 2000s indicated that α-adrenergic agonists are effective at reducing hypotension, and associated with less neonatal acidosis than ephedrine 6. National practice guidelines suggest the use of both ephedrine and phenylephrine for the management of hypotension; UK guidelines from 2011 state that: ‘Women who are having a caesarean section under regional anaesthesia should be offered intravenous ephedrine or phenylephrine, and volume pre-loading with crystalloid or colloid to reduce the risk of hypotension occurring during caesarean section’ 2. American guidelines from 2016 provide more detail: ‘Intravenous fluid preloading or co-loading: intravenous fluid preloading or co-loading may be used to reduce the frequency of maternal hypotension after spinal anesthesia for cesarean delivery; do not delay the initiation of spinal anesthesia in order to administer a fixed volume of intravenous fluid. Ephedrine or phenylephrine: either intravenous ephedrine or phenylephrine may be used for treating hypotension during neuraxial anesthesia; in the absence of maternal bradycardia, consider selecting phenylephrine because of improved fetal acid–base status in uncomplicated pregnancies’ 1. Surveys of clinical practice indicate that there has been a shift away from what was the almost universal use of ephedrine as the vasopressor of choice. In the UK, a 1999 survey found that 95% of respondents used ephedrine alone during caesarean section 7; in 2011, 89% of respondents used phenylephrine, and the remainder used metaraminol or ephedrine 8. A survey carried out in the USA in 2007 noted that 32% of respondents used ephedrine for vasopressor prophylaxis and treatment of hypotension, 26% and 23%, respectively, used phenylephrine, and the remainder used either agent according to maternal heart rate 9. Klöhr et al. found 15 different definitions of hypotension in 63 studies of hypotension following spinal or combined spinal-epidural anaesthesia for caesarean section, performed between 1999 and 2009 10. Definitions varied between those using an absolute blood pressure value, ranging from 80 mmHg to 100 mmHg, a decrease of 0–30% from a baseline or a combination of an absolute value and a percentage decrease. Some studies distinguished between severe hypotension and lesser (mild-moderate) degrees. All studies used the systolic arterial pressure (SAP) measured in the arm, in a variety of body positions; all but one 11 used the non-invasive oscillometric method. Baseline blood pressure readings were usually taken just before performing spinal anaesthesia, although occasionally at an earlier stage, such as on admission to the labour ward. The baseline was estimated from one, two or three replicate readings. Applying these different definitions to a cohort of women having elective caesarean section gave incidences for hypotension varying between 7.4% and 74.1% 10. The most common definitions of hypotension used in research studies were either ‘< 80% baseline’, or ‘< 100 mmHg OR < 80% baseline’ 10. A 1999 survey in the UK found that most consultant obstetric anaesthetists use a threshold of either 100 or 90 mmHg 7. The SAP is a less important variable than mean arterial pressure (MAP) as a determinant of organ perfusion; however, because methods used to measure blood pressure in routine clinical practice did not include the mean until recent decades, it is unlikely to be adopted for the definition of obstetric hypotension without considerably more supportive data. Most of the studies identified by Klohr et al. were at elective caesarean section; few included women in labour 12. Arterial pressure increases during labour; using baseline values taken in the antenatal period or at the start of labour was shown to reduce the incidence of recorded hypotension, defined as a decrease < 80% baseline value, after epidural analgesia 13. Many studies of hypotension at caesarean section did not include hypertensive women. The SAP threshold for pregnancy-induced hypertension or pre-eclampsia is > 140 mmHg 14. Nausea and vomiting are significantly more frequent during spinal anaesthesia for caesarean section than during non-obstetric surgery. The aetiology of this is multifactorial 15. Acute hypotension reduces cerebral perfusion, induces transient brainstem ischaemia and activates the vomiting centre. Transient cerebral hypoxia may occur, as studies using near-infrared spectroscopy (NIRS) show that hypotension is accompanied by a significant decrease in maternal regional cerebral blood volume, cerebral oxygen saturation and oxygenation 16. This is consistent with the observation that supplemental oxygen may relieve this nausea 17, 18. Spinal anaesthesia decreases splanchnic blood flow by approximately 20% 19, which may be accentuated by accompanying systemic hypotension. The resulting splanchnic hypoperfusion releases emetogenic factors such as serotonin from the gastro-intestinal tract. Finally, acute sympathetic blockade may cause unopposed vagal action and subsequent hyperactivity in the gastro-intestinal tract 20. Regardless of the aetiology, the use of prophylactic vasopressors significantly reduces the incidence of intra-operative nausea and vomiting during caesarean section 21. Dizziness and decreased levels of consciousness may follow severe and prolonged maternal hypotension, but are uncommon when blood pressure is The effect of hypotension on fetal during caesarean section in although research that a decrease of > in uterine blood flow in and in a Clinical have from studies that with and without hypotension, or duration of hypotension. of women with hypotension significant acidosis and hypotension of more than duration was associated with a significant in umbilical and of of hypotension may be more important than A transient decrease in blood pressure did not neonatal Apgar incidence of fluid or the need for oxygen in the Hypotension for less than did not neonatal more than of maternal hypotension was associated with at of important in acid–base during spinal anaesthesia for caesarean is the choice of vasopressor used to hypotension. from studies were recent clinical suggest that phenylephrine, as an is associated with neonatal acid–base than ephedrine Ephedrine has higher than phenylephrine, with umbilical arterial of and in doses this is associated with neonatal higher and and levels 5. These of fetal sympathetic metabolism by ephedrine the use of phenylephrine for during caesarean section in umbilical clinical in neonatal have not been these of phenylephrine ephedrine improved clinical in the is as The available studies show in the incidence of fetal acidosis when either ephedrine or phenylephrine was used to blood pressure during spinal anaesthesia for caesarean both in or those with acute fetal effects on and the of resulting in In such as bradycardia, may from The clinical to α- and β-adrenergic and and fetal effects Ephedrine not has but direct which the and duration of Ephedrine increases heart rate and by has a direct with at clinical at higher than it may with a in maternal et using found the of a phenylephrine to spinal hypotension to be et al. estimated the to spinal hypotension or nausea to be However, doses of this may be associated with increases in systemic and bradycardia, and a of 100 is more common this et al. found benefit when using doses of or phenylephrine to hypotension, in with doses of 100 The of phenylephrine to ephedrine for using is is a mixed α- and at doses used has both direct and it sympathetic it for to as a A recent used a of for is the by is a agonist, with with direct in higher heart than with doses of phenylephrine The for of hypotension is et al. found a of for In has for and at are more significant at higher is a mixed α- and β-adrenergic that has both direct and effects to the of and is available and fetal effects although it is a agent in a of and of this drug is that it does not The of clinical management is the of maternal blood on of the adverse effects of hypotension. However, from research studies that is an important The effect of spinal anaesthesia in a is a decrease in systemic to with a of There is a in heart rate and volume, which increases a spinal block to the sympathetic may be resulting in a of However, heart rate does not with block a of bradycardia, to is The aim of vasopressor treatment should to systemic which is best using with However, on doses of vasopressors to blood without other may to et al. used the and to measure in a of phenylephrine and ephedrine used in elective caesarean section. the decrease in systemic and hypotension more than there was between the percentage in heart rate and after the vasopressor of vasopressor that heart not is the best for when the is not measured et al. found in both maternal heart rate and measured with when three different of The rate both and heart rate by > This the that heart rate may indicate phenylephrine doses that are a to or hypotension and include methods to reduce and in the as as fluid the is for uterine is used to reduce with a of This of is associated with higher maternal SAP and and doses of phenylephrine than the but is in practice the is to is for may for the however, it be used during the period of before and at the before has been at that of the may be than at reducing hypotension at caesarean section but it is to during surgery. has been shown to be more effective than in hypotension, although a of that may on the and of used or to be of the lesser effect of with after spinal A between and did not show a in blood pressure found that to after spinal anaesthesia significant decrease in incidence of hypotension a found a in hypotension that an important between the studies was that crystalloid was used in the but in the crystalloid in the was performed using until a in this practice studies that it has very at reducing the incidence or severity of hypotension and is may be more effective at hypotension and vasopressor than pre-loading 63 or fluid a benefit pre-loading a recent a benefit on of vasopressor provided that a volume is under pressure during the after the spinal is more effective than crystalloid for of hypotension A of by in combination with prophylactic of phenylephrine, was associated with a significantly incidence of hypotension with a of as as less hypotension In a of colloid as effective as a of crystalloid both be to improve the provided by vasopressor have been as of hypotension, on of However, these have not been by more specific does not the frequency and severity of hypotension caesarean is associated with less hypotension than elective This is to be more to the of labour A wide variety of methods have been to the of hypotension after spinal anaesthesia These include that are not of routine and other baseline heart rate was found to be a of hypotension in studies but a of have not this > during a period in combined with > or > mmHg in SAP after from to for severe hypotension Baseline < 80% baseline < baseline Baseline > 90 for hypotension Baseline < 90 for hypotension > 100 Hypotension SAP < 100 mmHg significant hypotension hypotension as with symptoms hypotension SAP < 80 mmHg for clinically significant hypotension Baseline heart rate > Baseline methods not et al. found that was associated with a decrease in SAP than although the incidence of hypotension was not Some studies have occurring after the spinal as an of hypotension. and that provide an of hypotension, with a decrease in saturation hypotension by a et al. noted that in heart rate after the spinal were found in women who more severe hypotension a and available of hypotension is we suggest that there is a of hypotension the baseline heart rate is or there is a and recent of when non-invasive blood pressure is an in heart rate after the spinal may the of hypotension. A vasopressor with is the choice to reverse the effects of spinal phenylephrine has the most use However, and decreased associated with phenylephrine have research on and which have to β-adrenergic effects in to studies to phenylephrine in the of obstetric spinal anaesthesia have found that may be a to phenylephrine however, there are the use of such a agent in a such as the labour studies of and metaraminol A survey found that there are of phenylephrine available in the UK 8. The most common is a which is a of to a of 100 are the other used usually for rather than 8. should be in for of that in order to reduce the risk of drug should consider the of or noted a of definitions of hypotension are et al. that there were in the incidence of nausea and vomiting when SAP was at the baseline with < or < 80% baseline there were in neonatal umbilical blood We suggest that the aim should be to SAP of an measured baseline until of the with the of reducing the frequency and duration of of significant hypotension < 80% arterial pressure values < 80% should be usually with a vasopressor for blood pressure in practice for a period without or although this is unlikely to be in the of surgery. the other a is that the baseline blood pressure should be taken under to those after for with to studies a of in with to an baseline blood the oscillometric blood pressure et al. the to until three values of SAP were with a of < between The baseline pressure was to be the mean of those three and heart rate was as the mean of the three readings routine clinical most anaesthetists will one baseline of blood However, should be performed the value is higher than in a not to be or in a who is in it does not the from the and consider using this as the measure non-invasive blood pressure blood pressure is measured the is in one or other the non-invasive blood pressure should be on the to reduce from effects et al. performed a that included of prophylactic phenylephrine with vasopressor treatment hypotension treatment a benefit with to the incidence of hypotension both before and after as as nausea and phenylephrine in the of higher doses of phenylephrine when with the risk of maternal hypertension and were A subsequent to this prophylactic variable rate and phenylephrine with This that the was more effective at spinal hypotension, nausea and with clinical Most studies have a prophylactic of vasopressor with There are prophylactic phenylephrine with prophylactic phenylephrine A by et al. found that of phenylephrine at hypotension, nausea and vomiting when with a prophylactic of phenylephrine et al. when having a phenylephrine with those having an prophylactic of phenylephrine, by doses the phenylephrine used in these studies be to be a of 100 is more used both to and spinal hypotension the other a phenylephrine was with from blood pressure in the this it that a prophylactic phenylephrine is to and that the start of the in reducing the incidence of hypotension. In clinical vasopressor at the of a blood pressure will not be as as in research and will not be the the will be for delay in with subsequent hypotension, in with The is that the should be after the of the et al. prophylactic phenylephrine The having and to SAP > 80% with the having 100 In the and 100 higher incidences of hypertension to start an at a rate of and to variable rate are to fixed in order to the of phenylephrine a vasopressor is at a fixed rate after spinal there will be a delay in effective blood a of vasopressor after the spinal will more et al. that an phenylephrine of by an at SAP without any adverse effects work is to an for a prophylactic and that there is not a risk of hypertension and There are studies of used as a agent after the of an using an as the doses of ephedrine are to SAP < baseline when combined with a heart in order to blood pressure and There is to indicate the heart rate threshold in the absence of severe hypotension; clinicians should use clinical significant with hypotension, an or may be There is to routine use of for the of hypotension not used to hypotension, has a in hypotension and after spinal research is to vasopressor use a to the of vasopressor according to maternal blood There are of that may be when using The may an or a the the a fixed of vasopressor when it blood pressure a threshold for the the vasopressor by is varied in with the of hypotension, for between and 100 The may the vasopressor as a or as an in to blood pressure is more with doses of using of with phenylephrine, when in this include in blood pressure and higher for the and and levels for the blood pressure between the and of hypotension the use of a blood pressure may with delay and non-invasive blood pressure on the or have been including the the and These have the to blood pressure including et al. used for but a that phenylephrine or ephedrine according to heart to reduce found with phenylephrine This most recent included a that of doses blood pressure is with a This was to 80% of all SAP readings > 80% with maternal and fetal These suggest a for of vasopressor with non-invasive blood pressure to more of of these in the of to be increases during the of it has not been that ephedrine is than phenylephrine for neonatal in this ephedrine acidosis phenylephrine to be the best vasopressor choice in the of significant fetal caesarean section is for a in hypotension after spinal anaesthesia is with elective is to start a vasopressor at a rate than for elective in the of an should not delay other taken to of the The rate and severity of hypotension is after spinal and combined spinal epidural anaesthesia with combined spinal-epidural and epidural combined spinal-epidural and spinal provide with for vasopressor with severe pre-eclampsia less hypotension and have vasopressor during spinal anaesthesia, with women caesarean section These suggest that women with pre-eclampsia either have or are more to with women. There are few studies vasopressors in women with A the status of 15 women with severe pre-eclampsia having spinal anaesthesia for caesarean section for a maternal found that phenylephrine to spinal hypotension and systemic but did not significantly the volume or In a subsequent spinal anaesthesia for caesarean section in severe the maternal effects of ephedrine and phenylephrine were a colloid a of phenylephrine the spinal anaesthesia-induced in systemic heart rate and baseline more than 15 ephedrine A of ephedrine and phenylephrine for the treatment of hypotension after spinal anaesthesia in women with pre-eclampsia found in neonatal umbilical did a in women that included an of women with pre-eclampsia A recent has shown that in with severe pre-eclampsia and fetal fetal acid–base status is of the use of ephedrine phenylephrine to spinal hypotension These studies suggest that phenylephrine is the vasopressor to reverse the maternal by spinal anaesthesia in women with severe The of phenylephrine may be than in a prophylactic vasopressor may not be should be at a with the effect on blood pressure The choice of by or does not to neonatal The blood pressure for women with hypertension is of < mmHg are for SAP The aim should be to SAP to as a decrease in blood are frequently used in women with caesarean section in clinical In women with there is a during caesarean section with neuraxial with anaesthesia spinal anaesthesia is best in women with significant the and associated with spinal anaesthesia are with or fixed or neuraxial such as combined spinal-epidural or spinal anaesthesia, are There are studies the vasopressor to or hypotension after neuraxial anaesthesia in women with caesarean section. are on from and with caesarean section with neuraxial anaesthesia have been with phenylephrine by or non-invasive However, the phenylephrine should not be to all women with The of the specific and the by neuraxial anaesthesia, should the of the most vasopressor is the agent of choice in women with as it has in to ephedrine, may A decrease in systemic after neuraxial anaesthesia in the of fixed such as severe or are best or with by ephedrine may status in with phenylephrine may be in women with should be to increases in oxygen and blood the other ephedrine may be to phenylephrine in with should be may be as either are although or In the there are in of and and and may as a of antenatal with and be to of spinal to anaesthesia and should be non-invasive oscillometric blood pressure is this should be to not the or should the blood pressure as frequently as using the available at until having caesarean section need a of volume including vomiting and prolonged The of the of heart as an of in women with is now is an absolute to spinal anaesthesia for caesarean section; to in splanchnic and of blood the In this following spinal anaesthesia cause in and A of is usually for caesarean section. This may be or decreased for of but does not need to be for body is administer is an is although there are to less is to with to a for of with to a of with have been but there are be including and a and be taken to drug and with There is for the management of hypotension after spinal anaesthesia in resource-poor environments. A recent has the use of a fixed phenylephrine to provide with as This is an for the than a with a risk of In are on in resource-rich and for on is to with spinal anaesthesia without the of a vasopressor and an The vasopressor of is however, may mean that other may have to be These in order of other ephedrine and with a fluid such as is is an anaesthesia, and with 15 one the spinal is Spinal anaesthesia has been in because it in than However, spinal anaesthesia has the cause of maternal in because of hypotension or a combination of the two guidelines have been to anaesthetists or in the of block to and the of to spinal anaesthesia for caesarean section are This is the to spinal and to a lesser reduces systemic a in an in The are by an In the of or blood pressure the vasopressor should be to reduce the heart rate to the baseline not administer in to the blood pressure is to be this cause and in with uncommon caused by a rather than and in the body in to hypotension, the This should be by ephedrine, in to the there is a to vasopressors or the status of the should be heart and heart should be may include or on the Hypotension and are with other of and and decreased treatment to the is with including research is on the for a the for combined The more of that vasopressor may improve blood pressure after spinal The of such as in to important maternal and fetal for these are best used for research in order to and In non-invasive or including be indicated to hypotension be were and a variety of practice In the may to vasopressors We and for the of these and are of and this has has from has from has from for and for and has in has from and The for vasopressor at elective caesarean section under spinal-epidural phenylephrine to a of to a of phenylephrine of 100 In a of the phenylephrine an to the and with the vasopressor in the a or to intravenous crystalloid to a that has a with an the vasopressor to the to the and the crystalloid start colloid aim to before spinal non-invasive blood pressure the following values the baseline are the the vasopressor at a rate of between 15 and the to crystalloid by the to a pressure to the maternal SAP at the is for of the from the for at of the or a the vasopressor be although of effects of at the is and hypotension be the for of blood pressure to the there are symptoms such as nausea and vomiting with hypotension as the is for blood the of the the vasopressor should be and the should be to that there is vasopressor in the there is a for vasopressor at the of elective a of the should be with to the and fluid for management of hypotension after spinal anaesthesia for caesarean section in environments. of volume The vasopressor of is phenylephrine: A of options are such intravenous using of at non-invasive blood pressure the following vasopressor at the the to blood pressure until or the is crystalloid 15 by the to a pressure hypotension and to the SAP of baseline SAP and the heart rate of baseline heart as for hypotension the of nausea, is or is to not for readings before vasopressor in these the is for of the from the by at of the a or an is this or hypotension for a as

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References