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 treated promptly. The effect of postspinal hypotension on fetal physiology during caesarean section remains poorly characterised in humans, although animal research shows that a sustained decrease of > 60% in uterine blood flow results in bradycardia and acidaemia within 10 min in a previously uncompromised fetus 22. Clinical data have largely come from observational studies that separated groups with and without hypotension, or assessed duration of hypotension. Neonates of women with spinal-induced hypotension had significant acidosis 23, 24, and hypotension of more than 2 min duration was associated with a significant increase in umbilical venous oxypurines and lipid peroxides, suggestive of ischaemia–reperfusion injury 25. Duration of hypotension may be more important than severity. A transient ≥ 30% decrease in blood pressure did not affect neonatal Apgar scores, incidence of meconium-stained amniotic fluid or the need for oxygen therapy in the neonate 26. Hypotension for less than 2 min did not affect neonatal neurobehavioral outcomes 23, whereas more than 4 min of maternal hypotension was associated with neurobehavioral changes at 4–7 days of life 27. An important confounder in interpreting acid–base changes during spinal anaesthesia for caesarean delivery is the choice of vasopressor used to treat hypotension. Although results from early animal studies were conflicting, recent clinical trials clearly suggest that phenylephrine, given as an infusion, is associated with better neonatal acid–base balance than ephedrine 5, 28. Ephedrine has higher transplacental transfer than phenylephrine, with median umbilical venous/maternal arterial ratios of 1.13 and 0.17, respectively; in large doses this is associated with lower neonatal pH, higher base deficit, and increased lactate and catecholamine levels 5. These findings support activation of fetal sympathetic metabolism by ephedrine administration. Although the use of phenylephrine infusions for hemodynamic control during caesarean section results in optimum umbilical cord biochemical values, clinical differences in neonatal outcomes have not been demonstrated so far. Whether these biochemical advantages of phenylephrine over ephedrine translate into improved clinical outcomes in the compromised fetus is unclear as yet. The available studies show no difference in the incidence of fetal acidosis when either ephedrine or phenylephrine infusion was used to maintain blood pressure during spinal anaesthesia for emergency caesarean delivery, both in unselected (i.e. non-elective) cases 12, or specifically those with acute fetal compromise 29. Vasopressor drugs mediate their cardiovascular effects primarily through their actions on α1-, β1- and β2-adrenergic receptors, the relative stimulation of each receptor resulting in differing physiological effects. In addition, further changes, such as bradycardia, may result from reflex cardiovascular responses. The major clinical considerations relate to relative α- and β-adrenergic effects, onset time and duration, and fetal effects (Table 1). Ephedrine not only has mainly indirect adrenergic receptor activity but also exerts weak direct effects, which explains the comparatively slow onset and long duration of action. Ephedrine typically increases heart rate and contractility by cardiac β1-adrenergic receptor stimulation. Phenylephrine has a potent direct α1-effect, with virtually no β-effects at clinical doses. When given at higher than required doses, it may induce baroreceptor-mediated bradycardia with a consequent reduction in maternal cardiac output 11, 30, 31. George et al., using up-down sequential allocation, found the ED90 of a phenylephrine bolus to treat spinal hypotension to be 147 (95%CI 98–222) μg 32. Using similar methodology, Tanaka et al. estimated the ED95 to prevent spinal hypotension or nausea to be 159 (95%CI 122–371) μg 33. However, doses of this magnitude may be associated with increases in systemic vascular resistance and bradycardia, and a bolus dose of 100 μg is more common 32, 34. Supporting this conclusion, Mohta et al. found no benefit when using doses of 125 μg or 150 μg phenylephrine to treat hypotension, in comparison with doses of 100 μg 35. The potency ratio of phenylephrine to ephedrine for infusions, established using up-down sequential allocation, is 81:1 36. Metaraminol is a mixed α- and β-agonist although, at doses used clinically, α-effects predominate. It has both direct and indirect effects; it undergoes uptake into postganglionic sympathetic nerve endings, where it substitutes for noradrenaline to act as a weak false neurotransmitter 37. A recent comparative study used a dose ratio of 5:1 for metaraminol:phenylephrine 38. Noradrenaline is the primary catecholamine released by postganglionic adrenergic nerves. It is a potent α1-adrenergic agonist, with comparatively modest β-agonist activity. It causes marked vasoconstriction with some direct inotropic effects. Administration results in higher heart rates than with comparable doses of phenylephrine 39, 40. The ED90 for prevention of hypotension is 5.8 μg 41. Ngan Kee et al. found a dose ratio of 1:17 for noradrenaline:phenylephrine 39. In comparison, adrenaline (epinephrine) has high affinity for α1-, β1- and β2-adrenergic receptors. β-effects predominate at low doses, while α1-effects are more significant at higher doses. Mephentermine is a mixed α- and β-adrenergic receptor agonist that has both direct and indirect effects due to the release of noradrenaline and adrenaline. Limited information is available regarding placental transfer and fetal metabolic effects 42, although it is a popular agent in a number of low- and middle-income countries. An advantage of this drug is that it does not require multiple dilutions. The main focus of clinical management is the maintenance of maternal blood pressure, based on our understanding of the adverse effects of hypotension. However, evidence from research studies suggests that cardiac output is an important additional variable. The primary effect of spinal anaesthesia in a healthy woman is a decrease in systemic vascular resistance secondary to small artery vasodilation 43, 44, with a modest degree of venodilation 45. There is a compensatory baroreceptor-mediated increase in heart rate and stroke volume, which increases cardiac output 11, 31, 43, 46, 47. With a high spinal block to cervical levels, the pre-ganglionic sympathetic cardiac accelerator fibres may be blocked resulting in a failure of compensatory tachycardia. However, heart rate does not correlate well with block height; a pattern of sudden bradycardia, secondary to vasovagal (also termed Bezold–Jarisch) reflex activation, is well recognised 48. The aim of vasopressor treatment should be, therefore, to restore systemic vascular resistance, which is best achieved using agents with predominantly α-agonist activity. However, dependence on high doses of vasopressors to restore blood pressure, without other manoeuvres 49, may lead to low cardiac output. Dyer et al. used the calibrated LiDCOplus® monitor (LiDCO, Cambridge, UK) and transthoracic bio-impedance to measure cardiac output in a comparison of phenylephrine and ephedrine boluses used in elective caesarean section. Phenylephrine corrected the postspinal decrease in systemic vascular resistance and hypotension more effectively than ephedrine. Of note, there was good correlation between the percentage change in peak heart rate and peak cardiac output after the vasopressor bolus, independent of vasopressor type. They concluded that heart rate, not MAP, is the best surrogate for cardiac output when the latter is not being measured 31. Stewart et al. found dose-dependent reductions in both maternal heart rate and cardiac output, measured with suprasternal Doppler, when comparing three different infusion regimens of phenylephrine. The highest infusion rate reduced both cardiac output and heart rate by > 20%. This study also supports the hypothesis that reduced heart rate may indicate excessive phenylephrine doses that are causing a reduced cardiac output 30. Other measures to prevent or treat hypotension and haemodynamic instability include methods to reduce inferior vena cava compression and venous pooling in the legs, as well as intravascular fluid loading 45, 50-52. Once the woman is positioned supine for surgery, left uterine displacement is routinely used to reduce inferior vena cava compression, with a recommended angle of 15° 53, 54. This angle of table tilt is associated with higher maternal SAP and cardiac output and lower doses of infused phenylephrine than the unmodified supine position 55, but is seldom achieved in practice 56. If the table is tilted to 15°, lateral support is required for security. Adequately-applied tilt may make operating awkward for the obstetrician; however, it can be used during the period of preparation before surgery, and reduced at the last moment before surgery if haemodynamic stability has been achieved at that point. Manual displacement of the uterus may be better than left lateral tilt at reducing hypotension at caesarean section 51, but it is difficult to sustain during surgery. Leg compression has been shown to be more effective than no leg compression in preventing hypotension, although a high level of heterogeneity suggests that its effectiveness may depend on the type and intensity of compression used (bandages, inflatable boots or antithromboembolic stockings) 50. Venous compression seems to be of limited effectiveness, possibly reflecting the lesser effect of venodilation compared with arteriolar dilation after spinal anaesthesia. A comparison between thromboembolic deterrent (TED) stockings and sequential compression boots/leggings did not show a difference in blood pressure changes 57. One study found that leg elevation to 30° after spinal anaesthesia reported no significant decrease in incidence of hypotension 58, whereas a larger study found a similar numerical reduction in hypotension that reached statistical significance 59; an important difference between the studies was that i.v. crystalloid pre-load 20 ml.kg−1 was used in the former, but none in the latter. Intravenous crystalloid pre-loading, first described in the 1960s, was performed using ever-increasing volumes until a landmark study in 1993 challenged this practice 60. Further studies confirmed that it has very limited effectiveness at reducing the incidence or severity of hypotension 50, and is no longer recommended 61, 62. Crystalloid coloading may be more effective at decreasing hypotension and vasopressor requirements than pre-loading 63 or no fluid 64. Although a meta-analysis suggested no benefit vs. pre-loading 65, a recent analysis suggests a moderate additional benefit on top of vasopressor prophylaxis, provided that a sufficient volume is infused under pressure during the first 5–10 min after the spinal 66. Colloid pre-load is more effective than crystalloid pre-load for prevention of hypotension 50, 67. A 500-ml pre-load of 6% hydroxyl-ethyl starch (HES; 130/0.4) followed by 500 ml Ringer's lactate, in combination with prophylactic boluses of phenylephrine, was associated with a significantly lower incidence of hypotension compared with a 1000-ml pre-load of Ringer's lactate (37% vs. 55%, respectively) as well as less symptomatic hypotension (4% vs. 14%, respectively) 68. In general a 500-ml pre-load of colloid appears as effective as a 1000-ml coload of crystalloid 69. Thus, both fluid-loading techniques can be recommended to improve the haemodynamic stability provided by vasopressor prophylaxis. Individual patient characteristics have been suggested as predictors of hypotension, based on multivariate analyses of population data 70, 71. However, these findings have not been replicated by more specific prospective investigations. Body mass index does not affect the frequency and severity of hypotension 72-74. Emergency caesarean is associated with less hypotension than elective surgery 70. This is likely to be more particularly related to the presence of labour 12, 75, 76. A wide variety of methods have been described to predict the development of hypotension after spinal anaesthesia (Table 2) 73, 77-93. These include basic cardiovascular variables, cardiovascular measurements that are not part of routine monitoring, complex processed cardiovascular indices, postural manipulations and other methods. Pre-operative baseline heart rate was found to be a useful predictor of hypotension in several studies 80, 81, 89, but a number of others have not supported this 73, 79, 88. Supine stress test; HR increase > 10% during a 5-min period in supine position; combined with leg flexion while supine Tilt test – HR increase > 10 beats.min−1 or > 10 mmHg fall in SAP after moving from left lateral to sitting position Sensitivity 75%, specificity 82%, PPV 86%, NPV 69% for severe hypotension Not predictive (no positive results) Orthostatic challenge – 5 min standing Baseline HR Mild – MAP < 80% baseline Marked – MAP < 70% baseline Not predictive Baseline HR > 90 beats.min−1 – PPV 83% for marked hypotension Baseline HR < 90 beats.min−1 – NPV 75% for marked hypotension HRV – point correlation dimension HR > 100 beats.min−1 Hypotension – SAP < 100 mmHg Clinically significant hypotension – hypotension as above with symptoms Severe hypotension – SAP < 80 mmHg Crystalloid pre-load: Sensitivity 69%, specificity 92%, PPV 90%, NPV 73% for clinically significant hypotension Perfusion index 3.5 Baseline HR Sensitivity 81%, specificity 86%, PPV 89%, NPV 76% Not predictive Pre-operative heart rate Perfusion index Pleth variability index LF/HF ratio HRV entropy LF/HF ratio > 2.0 Baseline HR Body mass index Sensitivity 52%, specificity 76%, PPV 66%, NPV 64% Other methods not predictive Orbach-Zinger et al. found that high pre-operative anxiety was associated with a greater decrease in SAP than low anxiety, although the incidence of hypotension was not reported 94. Some studies have investigated changes occurring after the spinal block, as an indicator of impending hypotension. Berlac and Rasmussen suggested that NIRS could provide an early warning of hypotension, with a ≥ 5% decrease in saturation preceding hypotension by a median (IQR) 81 (3–281) s 95. Hanss et al. noted that greater changes in heart rate variability after the spinal were found in women who then developed more severe hypotension 96. Until a definitive and widely available method of predicting hypotension is identified, we suggest that there is a raised likelihood of developing hypotension if the baseline heart rate is high or there is a clear and recent history of supine intolerance/supine hypotensive syndrome. Furthermore, when intermittent non-invasive blood pressure measurement is being used, an increase in heart rate after the spinal local anaesthetic injection may precede the recognition of hypotension. A vasopressor with predominantly α-agonist activity is the correct choice to reverse the circulatory effects of spinal anaesthesia; phenylephrine has the most evidence supporting its use 97. However, concerns about reflex bradycardia and decreased cardiac output associated with phenylephrine have prompted research on noradrenaline and metaraminol, which might have some advantages due to their mild β-adrenergic effects in addition to α-effects 38, 39. Preliminary studies comparing noradrenaline to phenylephrine in the setting of obstetric spinal anaesthesia have found that noradrenaline may be a reasonable alternative to phenylephrine 39, 40, 98; however, there are concerns about the use of such a potent agent in a non-intensive care setting such as the labour ward 99, 100. Further studies of noradrenaline and metaraminol are, therefore, awaited. A national survey found that there are multiple formulations of phenylephrine available in the UK 8. The most common presentation is a 1-ml ampoule containing 10 mg, which is diluted into a 100-ml bag of saline to produce a final concentration of 100 μg.ml−1 (Appendix 1). Solutions containing 50 μg.ml−1 are the only other commonly used concentration, usually for bolus administration rather than infusion 8. Clear systems should be in place for dilution of ampoules that contain high-concentration potent vasopressors, in order to reduce the risk of drug error. Anaesthetic departments should consider the benefits vs. risks of sourcing dilute ampoules, or prefilled syringes. As noted earlier, a number of definitions of hypotension are currently used. Ngan Kee et al. showed that there were marked improvements in the incidence of nausea and vomiting when SAP was maintained at the baseline level, compared with < 90% or < 80% baseline 49; there were also measurable, albeit small, improvements in neonatal umbilical cord blood gas status. We suggest that the aim should be to maintain SAP ≥ 90% of an accurately measured baseline until delivery of the neonate, with the intention of reducing the frequency and duration of episodes of significant hypotension < 80% baseline. Systolic arterial pressure values < 80% should be treated expeditiously, usually with a vasopressor bolus injection. Guidelines for blood pressure measurement in general medical practice suggest, for accuracy, a 5-min period without movement or speaking 101, although this is unlikely to be achieved in the situation of impending surgery. On the other hand, a potentially conflicting requirement is that the baseline blood pressure should be taken under similar conditions to those after spinal, for example, with regard to position. Research studies demand a high degree of accuracy in measurement, especially with regard to an accurate baseline blood pressure. For the oscillometric blood pressure method, Ngan Kee et al. set the device to repeat measurements every 1–2 min until three consecutive values of SAP were achieved with a difference of < 10% between them. The baseline pressure was considered to be the mean of those three readings, and heart rate was calculated as the mean of the three concurrent readings 39. During routine clinical practice, most anaesthetists will only take one baseline measurement of blood pressure. However, repeated measurements should be performed if the value is higher than expected in a woman not known to be hypertensive, or in a woman who is in labour. If it does not settle, check the latest reading from the medical notes, and consider using this as baseline. After the spinal, measure non-invasive blood pressure every minute. If blood pressure is being measured while the woman is in one or other lateral position, the non-invasive blood pressure cuff should be placed on the dependent arm to reduce error from hydrostatic effects 102. Heesen et al. performed a meta-analysis that included comparisons of prophylactic phenylephrine infusion vs. placebo infusion with vasopressor treatment if hypotension developed (reactive management). Prophylactic treatment demonstrated a benefit with regard to the incidence of hypotension both before and after delivery, as well as nausea and vomiting. Prophylactic phenylephrine infusions resulted in the administration of higher doses of phenylephrine overall, when compared with reactive treatment, while the risk of maternal hypertension and bradycardia were similar 103. A randomised, controlled trial, published subsequent to this meta-analysis, compared prophylactic variable rate infusion and rescue phenylephrine boluses, with rescue boluses alone. This demonstrated that the infusion was more effective at preventing spinal hypotension, nausea and vomiting, with fewer clinical interventions 104. Most studies have compared a prophylactic infusion of vasopressor with reactive administration. There are limited data comparing prophylactic phenylephrine infusions with prophylactic phenylephrine boluses. A study by das Neves et al. found that continuous infusion of phenylephrine appeared superior at preventing hypotension, nausea and vomiting when compared with a prophylactic dose of 50 μg phenylephrine 105. Sen et al. reported similar results when comparing patients having a phenylephrine infusion with those having an initial prophylactic dose of 50 μg phenylephrine, followed by intermittent 50 μg doses 106. Of note, the phenylephrine boluses used in these studies would be considered to be small; a dose of 100 μg is more widely used both to prevent and treat spinal hypotension 34, 49. On the other hand, a high-dose (120 μg.min−1), fixed-rate phenylephrine infusion was comparable with 120 μg boluses, apart from better early blood pressure control in the latter group 107. From this evidence, it appears that a prophylactic phenylephrine infusion is superior to bolus administration only, and that delaying the start of the infusion could limit its efficacy in reducing the incidence of hypotension. In clinical practice, vasopressor administration at the point of recording a low blood pressure will not be as meticulous as in research studies, and will not be done ‘on the clock’. Therefore, the tendency will be for delay in bolus treatment, with subsequent hypotension, in comparison with infusion. The corollary is that the infusion should be started prophylactically immediately after the insertion of the spinal. Allen et al. studied four prophylactic fixed-rate phenylephrine infusions. The groups having 25 μg.min−1 and 50 μg.min−1 had fewer physician interventions to maintain SAP > 80% baseline, compared with the group having 100 μg.min−1. In addition, the 75 μg.min−1 and 100 μg.min−1 groups had higher incidences of reactive hypertension 108. It seems preferable to start an infusion at a rate of 25–50 μg.min−1, and titrate to response. Physician-controlled variable rate infusions are preferable to fixed rate, in order to limit the total dose of phenylephrine infused. If a vasopressor infusion is commenced at a fixed rate after spinal insertion, there will be a delay in achieving effective blood levels, whereas adding a bolus dose of vasopressor immediately after the spinal will allow more rapid effect. Kuhn et al. demonstrated that an initial phenylephrine bolus of 0.25 μg.kg−1, followed by an infusion at 0.25 μg.kg.min−1, maintained SAP without any adverse effects 45. Further work is required to identify an optimum dose for a prophylactic bolus, and ensure that there is not a risk of reactive hypertension and bradycardia. There are no comparative studies of drugs used as a second-line agent after the initial administration of an α-agonist. When using an α-agonist as t
