Use of phenylephrine in the treatment of septic shock and SA-induced hypotension

Phenylephrine is a vasopressor used for the maintenance of blood pressure in the operating theatre and in the treatment of hypotension associated with septic shock in some cases. Prophylactic phenylephrine infusion is effective in preventing spinal anaesthesia (SA)-induced hypotension during caesarean delivery and has been shown to be an effective method of reducing SA-induced hypotension in the elderly undergoing surgery. 1

Use of phenylephrine in treating septic shock

Initial management of patients with septic shock requires rapid intervention to maintain mean arterial pressure (MAP) of ≥65 mm Hg and cardiac output while addressing the infection with antimicrobial therapy and source control. Patients who fail to respond to aggressive fluid resuscitation are candidates for vasopressor or inotropic therapy to restore and maintain blood pressure.2

Current guidelines recommend norepinephrine as the first line vasopressor agent to increase peripheral vascular resistance and to preserve organ perfusion following adequate volume therapy. 3 However, this recommendation is based only on moderate evidence and lacks compelling data to suggest that any agent other than NE should be used as first line therapy. Meta-analyses in 2015 and 2016 consistently reported no difference in clinical outcomes, including mortality, when comparing NE with epinephrine, phenylephrine, and vasopressin.5

A study by Morelli, et al, 5 that compared the haemodynamic effects of phenylephrine and norepinephrine infusion in the early phases of septic shock, found the administration of phenylephrine as a first-line vasopressor agent to be effective in increasing the MAP without compromising gastrointestinal and hepatosplanchic perfusion as compared with NE.

In the randomised, double-blind, controlled clinical trial, 32 patients who fulfilled the criteria of septic shock, presenting with a MAP of < 65 mmHg despite appropriate volume resuscitation pulmonary artery occlusion pressure (PAOP) = 12 to 18 mmHg and central venous pressure = 8 to 15 mmHg were randomised to receive either phenylephrine (N=16) or norepinephrine infusion (N=16) for 12 hours. The main endpoint of the study was the modifications of the PDR and CBI after phenylephrine administration as compared with the norepinephrine group.5

The major findings of the study were that, when administered as a first-line vasopressor agent in septic shock patients, phenylephrine did not worsen hepatosplanchnic perfusion as compared with NE, had similar effects as NE on cardiopulmonary performance and global oxygen transport, and was less effective than NE to counteract sepsis-related arterial hypotension as reflected by the higher dosages required to achieve the same goal MAP.5

In another study that compared phenylephrine and NE in the management of dopamine-resistant septic shock in 54 patients, phenylephrine infusion was found to be comparable to norepinephrine in reversing hemodynamic and metabolic abnormalities of sepsis patients, with an additional benefit of decreasing heart rate and improving Stroke Volume Index. 6

Use of phenylephrine to prevent SA-induced hypotension

While phenylephrine has been shown to be effective in preventing SA-induced hypotension during caesarean delivery, studies have also been conducted to evaluate its efficacy and safety to prevent SA-induced hypotension after orthopaedic surgery.1 SA-induced hypotension is common in elderly patients, which increases the risk for hypoperfusion of organs with an already decreased functional reserve.1 Routine bolus crystalloid fluids for the prevention of hypotension after SA is not always effective. Hypotension in these patients can quickly lead to volume overload and signs of congestive heart failure (CHF) when the effects of SA wears off. A vasopressor during orthopaedic surgery in elderly patients is therefore indicated.1

In a prospective randomised double-blind, placebo controlled study that included 54 patients >60 years undergoing elective lower limb surgery under spinal anaesthesia, patients were randomised to receive 100-μg/mL solution of
phenylephrine solution at 1 mL/min after placement of SA (28 patients) while the control group (26 patients) received 0.9% isotonic sodium chloride solution. Hypotension was defined by a 20% decrease and hypertension as a 20% increase from baseline MAP. In the patients receiving phenylephrine, MAP was higher than in the control group (92 ± 2 vs 82 ± 2 mm Hg, mean ± SD, P< .001). The number of hypotensive episodes per patient was higher in the control group, but the number of hypotensive patients was similar between groups (19 [73%] vs 20 [71%], P= 1). The time to onset of the first hypotension was shorter in the control group (3 [1-13] vs 15 [1-95] minutes, P= .004). The proportion of patients without hypotension (cumulative survival) was better in the phenylephrine group P (P= .04). The number of hypertensive episodes per patient and the number of bradycardic episodes per patient were similar between groups (P= not significant). 1

The researchers concluded that prophylactic phenylephrine infusion is an effective method of reducing SA-induced hypotension in the elderly. Compared with the control group, it delayed the time to onset of hypotension and decreased the number of hypotensive episodes per patient. 1

In a study comparing phenylephrine with ephedrine in the prevention of hypotension in patients undergoing hip fracture surgery, 92 patients were randomised to either receive an IV bolus of 10 mg ephedrine or an IV bolus of 50 µg phenylephrine. 6. In the phenylephrine group, the frequency of hypotension was significantly lower in MAP, systolic and diastolic pressure in 3, 6, and 9 min after spinal anaesthesia (P = 0.002, P = 0.001) than in the ephedrine group, indicating that phenylephrine was better to prevent hypotension during hip fracture surgery with spinal anesthesia. A higher frequency of hypotension was also observed in the ephedrine group.1

References:

1.  Ferré F, et al. Prophylactic phenylephrine infusion for the prevention of hypotension after spinal anesthesia in the elderly: a randomized controlled clinical trial. Journal of Clinical Anesthesia, Volume 35, December 2016, Pages 99-106.

2.  Pollard S, et al Vasopressor and Inotropic Management Of Patients With Septic Shock. Pharmacy and Therapeutics. July 2015; 40(7): 438-442, 449-450.

3. Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA.  016;315(8):801-810.

4. Sacha GL, et al. Vasoactive Agent Use in Septic Shock: Beyond First-Line Recommendations. Pharmacotherapy. 2019 Mar;39(3):369-381

5. Morelli A, et al. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomised, controlled trial. Crit Care. 2008; 12(6): R143.

Source: Med Brief Africa, 2 December 2019 (https://medbriefafrica.co.za/use-of-phenylephrine-in-the-treatment-of-septic-shock-and-sa-induced-hypotension/)