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Pharmacological Interventions for Orthostatic Hypotension

Two studies have examined pharmacological interventions (midodrine and methylprednisolone) for the treatment of OH. While midodrine hydrochloride in acute OH has also been studied in case report format (Barber et al., 2000; Mukand et al., 2001), these studies did not meet SCIRE inclusion criteria. Several other pharmacological agents have been studied in the chronic SCI population, including fludrocortisone, dihydroergotamine, ephedrine, L-threo-3,4-dihydroxyphenylserine (LDOPS), nitro-L-arginine methyl ester (L-NAME), although little evidence exists regarding their use for OH in chronic SCI (refer to SCIRE Orthostatic Hypotension rehabilitation evidence chapter).

Table 4. Pharmacological Management of Orthostatic Hypotension during Acute SCI

Author Year


PEDro Score

Research Design

Sample Size

Phillips et al., (2014b)


RCT crossover




Population: Mean age=30.7yr; Gender: males=7, females=3; Level of injury: C4-T5; Severity of injury: AIS A-B.

Population demographics as stated above are for SCI patiently only. This study also included 10 age- and sex-matched able-bodied control individuals.

Intervention: Patients were progressively tilted from supine to 30°, 45°, and 60°; this tilting procedure was conducted over 2 days, during which SCI patients were administered 10 mg of midodrine (treatment) or given no treatment (control, baseline measure) in a randomized order.

Outcome Measures: Resolution of orthostatic hypotension (OH), Mean Arterial Pressure (MAP).

Chronicity: 8 patients were <1yr post injury (6.5-11wk); 2 patients were >1yr post injury (144-324wk).

1.     Midodrine lessened the decline in MAP from 0 to 60s after tilt; Posterior cerebral artery blood velocity did not decline as much 30-60s after tilt in the treatment group compared to the control group (p<0.05).

2.     Midodrine led to a 59% improvement in orthostatic tolerance in the treatment group compared to the control group (p<0.01).

Krstacic et al., (2016)


Prospective Controlled Trial


Population: Tetraplegia.

Interventions: Patients received either methylprednisolone or no treatment. The methylprednisolone group received an initial bolus of 30 mg/kg followed by 5.4 mg/kg every hour for 23hr. All patients had heart rate variability monitored by an electrocardiogram holter monitor.

Outcome Measures: Heart rate frequency domains, heart variability time domains.

Chronicity: Treatment was initiated within 8hr of injury.

1.     There were no statistically significant results between groups on measures of heart rate variability.

Two studies examined the impact of pharmacological management on OH during acute SCI. Phillips et al. (2014) conducted a RCT examining the effectiveness of midodrine for OH in10 SCI patients, the majority of which had acute injuries (6.5-11 weeks after injury). This study did also include two patients with chronic SCI who were 144-324 weeks after injury. Patients were subjected to a tilt-table procedure in which they were progressively tilted from supine position to 30°, 45°, and 60° angles. This procedure was conducted over two days, during which time the SCI patients were randomly assigned to receive 10 mg of midodrine orally, or no treatment (baseline measure). Improvement in orthostatic tolerance was observed in 59% of patients who received midodrine; this was a significant improvement compared to those who received no treatment (p<0.01). A more recent prospective controlled trial by Krstacic et al. (2016), examined the effects of methylprednisolone on heart rate in an SCI population. However, this study found no significant differences between groups over a treatment period of 23 hours. Heart rate variability was monitored via an electrocardiogram holter monitor.


There is level 2 evidence (from one RCT crossover; Phillips et al., 2014) that midodrine hydrochloride leads to improved orthostatic tolerance in acute SCI patients.

There is level 2 evidence (from one PCT; Krstacic et al., 2016) that methylprednisolone may have no effects on heart rate variability in SCI populations.

Midodrine hydrochloride may be effective for the management of orthostatic hypotension during the acute phase post SCI.

Methylprednisolone appear to not be effective for the management of heart rate variability post SCI.