Triple H therapy
The combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy) is often utilized to prevent and treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH).
Although this paradigm has gained widespread acceptance since 1985, the efficacy of triple-H therapy and its precise role in the management of the acute phase of SAH remains uncertain. In addition, triple-H therapy may carry significant medical morbidity, including pulmonary edema, myocardial infarction, hyponatremia, renal medullary washout, indwelling catheter-related complications, cerebral hemorrhage, and cerebral edema 1).
This practice is based on low level evidence.
see Induced hypertension for vasospasm.
Many older treatment schemes for CVS included so-called “triple- H” therapy (for Hypervolemia, Hypertension, and Hemodilution) 2). This has given way to “hemodynamic augmentation” consisting of maintenance of euvolemia and induced arterial hypertension 3). While potentially confusing, this has now sometimes been referred to as Triple-H therapy 4).
Inducing HTN may be risky with an unclipped ruptured aneurysm. Once the aneurysm is treated, initiating therapy before CVS is apparent may minimize morbidity from CVS 5) 6).
Use fluids to maintain euvolemia.
Administer pressors to increase SBP in 15% increments until neurologically improved or SBP of 220 mm Hg is reached.
○ start at 2.5 mcg/kg/min (renal dose)
○ titrate up to 15–20 mcg/kg/min
○ start at 1–2 mcg/min
○ titrate every 2–5 minutes: double the rate up to 64 mcg/min, then increase by 10 mcg/min
● neosynephrine (phenylephrine): does not exacerbate tachycardia
○ start at 5 mcg/min
○ titrate every 2–5 minutes: double the rate up to 64 mcg/min, then increase by 10 mcg/min up to a max of 10 mcg/kg
● dobutamine: positive inotrope
○ start at 5 mcg/kg/min
○ increase dose by 2.5 mcg/kg/min up to a maximum of 20 mcg/kg/min
Complications of hemodynamic augmentation:
● intracranial complications 7)
○ may exacerbate cerebral edema and increase ICP
○ may produce hemorrhagic infarction in an area of previous ischemia
● extracranial complications
○ pulmonary edema in 17%
○ 3 rebleeds (1 fatal)
○ MI in 2%
○ complications of PA catheter: 8)
– catheter related sepsis: 13%
– subclavian vein thrombosis: 1.3%
– pneumothorax: 1%
– hemothorax: may be promoted by coagulopathy from dextran 9).
In a study of Engquist et al. from Uppsala, CBF was assessed by bedside xenon CT at days 0-3, 4-7, and 8-12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. Cerebral blood flow measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.
In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1-33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2-46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a Lactate to Pyruvate Ratio of 26.9 (IQR 22.9-48.5) at baseline and 31.6 (IQR 22.4-35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.
Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation 10).
An audit of the SAH patient charts was performed. A total of 508 fluid measurements were performed in 41 patients (6 with delayed cerebral ischaemia; DCI) during 14 days of observation.
Underestimating for intravenous drugs was the most frequent error (80.6%; 112), resulting in a false positive fluid balance in 2.4% of estimations. In 38.6% of the negative fluid balance cases, the physicians did not order additional fluids for the next 24h. In spite of that, the fluid intake was significantly increased after DCI diagnosis. The mean and median intake values were 3.5 and 3.8l/24h respectively, although 40% of the fluid balances were negative. The positive to negative fluid balance ratio was decreasing in the course of the 14 day observation.
This study revealed inconsistencies in the fluid orders as well as mistakes in the fluid monitoring, which illustrates the difficulties of fluid therapy and reinforces the need for strong evidence-based guidelines for hypervolemic therapy in SAH 11).