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Pharmacological Interventions for Neurogenic Shock

Studies addressing the pharmacological management of neurogenic shock in acute SCI are limited. One study investigated the effect of pseudoephedrine as an adjuvant therapy in acute SCI patients (Wood et al., 2014). Pseudoephedrine is a stimulant and amphetamine.

Table 1. Pseudoephedrine as an Adjunctive Therapy for Treatment of Neurogenic Shock

Author Year

Country

Research Design

Sample Size

MethodsOutcomes
Readdy et al., 2015

United States

Cohort

N=34

Population: Mean age: 61.53yr; Gender: males=28, females=6; Mean injury severity score=23.52; Mean ICU LOS (days)=11.67.

Interventions: Vasopressor administration

Outcome Measures: American Spinal Injury Association grade improvement, vasopressure administration, complications.

1.     Nineteen patients (56%) saw an improvement of at least one ASIA scale score.

2.     Thirty-one patients had dopamine administered, 22 had phenylephrine, 27 had dopamine administered first, 7 had phenylephrine administered first, 18 patients had 2 vasopressors, and 12 had 2 or more vasopressors concurrently.

3.     90% of patients over 55 years old experienced complications, this is compared to 52% of younger patients. This effect was seen regardless of injury severity, ASIA scale score, and steroid administration.

4.     Cardiogenic complications occurred in 26 patients, while the second highest complication was respiratory failure and urinary tract infections.

Phillips et al., (2014a)

Canada

PCT

N=16

Population: Mean age=30yr (SCI Group), mean age=26yr (Able-bodied, AB Group); Gender: males=7, females=1 (SCI Group), males=7, females=1 (AB Group); Level of injury: C4-C7; Severity of injury: AIS A-B.

Intervention: Patients with SCI (SCI Group) were given 10 mg of midodrine and compared to able-bodied controls (AB Group) who were not given treatment. Patients were transferred to a tilt table and tilted from supine to 30o, 45o, and 60o angles; hemodynamic data was collected at each position. This tilting procedure was conducted over 2d, during which SCI patients were administered midodrine or given no treatment in a randomized order.

Outcome Measures: Baroreflex Sensitivity (BRS) and Common Carotid Artery (CCA) stiffness.

Chronicity: 7 SCI patients were 6.5-11 weeks post injury, 1 SCI patient was 144wk post injury.

1.     Arterial stiffness was elevated in SCI patients when in the upright position compared to AB controls (p<0.05).

2.     In the SCI Group, there was a significant negative association between BRS and arterial stiffness in the upright position (p=0.03); no significant relationship was found in the AB Group (p=0.15).

3.     Reduced BRS is related to increased arterial stiffness in SCI patients.

4.     Midodrine led to increased BP and reduced HR in SCI patients compared to AB controls.

5.     No changes in BRS or CCA parameters occurred after midodrine administration in SCI patients.

Wood et al., (2014)

USA

Case Series

N=38

Population: Mean age=38.8 yr; Gender: males=29, females=9; Level of injury: C1-C7, below C7; Severity of injury: mean Injury Severity Score (ISS)=35.

Intervention: Retrospective review of SCI patients admitted to an Intensive Care Unit (ICU) who were administered pseudoephedrine for more than one day or were receiving vasopressor support and/or atropine.

Outcome Measures: Discontinued vasopressor use, decreased use of atropine, reduced bradycardic episodes.

Chronicity: Mean ICU length of stay was 39d.

1.     Pseudoephedrine success was observed in 31 of 38 (82%) patients.

2.     Mean duration of pseudoephedrine therapy was 32d.

Discussion

A case series conducted by Wood et al. (2014) investigated the effectiveness of pseudoephedrine as an adjunctive therapy option to the use of vasopressors and atropine in acute SCI. Patients who were administered pseudoephedrine for more than one day during their hospital stay or who received vasopressor support and/or atropine were retrospectively reviewed. Treatment with pseudoephedrine was considered successful based on discontinued vasopressor and atropine use, or a reduction in bradycardic episodes following pseudoephedrine administration; effectiveness was observed in 31 of 38 (82%) of patients. The mean duration of pseudoephedrine therapy was 32 days on average. A cohort study by Readdy et al. (2015) found that patients over the age of 55 had higher rates of complications. Cardiac complications occurred in 26% of patients. Complications regardless of severity of injury and vasopressor use.

 

Phillips et al. (2014) conducted a prospective controlled study to examine the association between baroreflex sensitivity (BRS) and common carotid artery (CCA) stiffness, as well as the influence of midodrine on BRS and arterial stiffness. The majority of SCI participants included in this study were within 6.5-11 weeks of injury, although 1 participant had chronic SCI and was 144 weeks after injury at the time of the study. Arterial stiffness was elevated in SCI patients compared to able-bodied controls when in the upright position (p<0.05). BRS and arterial stiffness were found to be negatively associated in the upright position in SCI patients (p=0.03), indicating that reduced BRS is related to increased arterial stiffness following SCI. Midodrine administration led to increased BP and reduced HR in SCI patients; however, it had no effect on BRS or CCA parameters.

Conclusion

There is level 4 evidence (from one case series study; Wood et al., 2014) that pseudoephedrine may be an effective adjuvant for the treatment of neurogenic shock in acute SCI patients; however, this pharmacological agent may require up to one month for effectiveness.

There is level 2 evidence (from one PCT; Phillips et al., 2014a) that midodrine may lead to increased blood pressure and reduced heart rate in SCI populations compared to health controls.

  • Pseudoephedrine may be an effective adjuvant for the treatment of neurogenic shock during the acute phase post SCI; however, pseudoephedrine may require up to one month for effectiveness and may result in higher complication rates for older patients.