Total Body Water

Total Body Water and Volume

Urea is freely permeable so elevated BUN can create a hyperosmotic condition but not a hypertonic situation. Measured osmolality is done via the freezing method, whereas calculated = 2 x [Na+] + [BUN]/2.8 [glucose]/18. Normal value is 286 +/- 4. A normal osmolal gap can be as high as 10 mOsm/kg [NEJM 310: 102, 1984; J Crit Illness 11: 720, 1996]. Osmolal gaps have been recommended to distinguish acute (normal) from chronic (osmolal gap) renal failure but is rarely used for this purpose [Ann Intern Med 98: 481, 1983]


Tonicity (effective osmolality) is different in that it only takes into account elements that do not cross a barrier (for neurologic patients, the blood brain barrier). Urea nitrogen, as it is freely permeable, is not included.

Tonicity ≅ 2 x [Na+] + [glucose]/18

Mannitol and ARF

A series of 8 patients who went into ARF s/p mannitol showed failure within 3.5 +/- 1.1 days after mannitol doses of 189 +/- 64 g daily (626 +/- 270 g total). Peak osmolal gap was 74 +/- 39 mOsm/kg water. In patients with normal baseline renal function ARF developed after receiving total mannitol doses of 1171 +/- 376 g. The peak osmolal gap was 107 +/- 17 (ie health patients tolerate a measured serum osmolality 376 or a osmole gap of ≥ 90). In those with underlying renal compromise, renal function worsened after a total mannitol dose of 295 +/- 143 g [Medicine (Baltimore) 69: 153, 1990]. Much of this is refuted by a recent retrospective study of 98 patients on mannitol at WUSTL, the multivariate analysis of which showed that APACHE II and history of CHF were the only predictive factors leading to mannitol-induced renal failure. Osmolality gap and mannitol dose had no correlation. Furthermore, all cases of MI-RF reversed [J Neurosurgery 103: 244, 2005]


Osmoreceptors in the anterior hypothalamus provide the stimulus for vasopressin (ADH) release [J Lab Clin Med 101: 351, 1983] starting at a threshold of 280 mOsm/L. In the absence of ADH, serum osmolarity can still be maintained as long as consciousness permits thirst and consumption of fluids. note that ADH can also be stimulated by increased sympathetic tone (pain, hemorrhage, hypovolemia [Am J Physio 236: F321, 1979]), elevated ICP [J Neurosurg 46: 627, 1977; Acta Neurochir 77: 46, 1985; Acta Neurol Scand 74: 81, 1986], nausea, opiates, and carbamazepine. Hypovolemia is a strong enough stimulus that ADH will be released at < 280 mOsm/L [Fed Proc 27: 1132, 1948]

Water requirements in the standard surgical patient are 30-35 cc/kg/day. Fever increases insensible loss by 300 cc/day/C. In critically ill patients, maintenance water requirements may be reduced to as low as 20-25 cc/kg/day (intubation/inhalation of humidified air, tissue catabolism, increase AVP levels all contribute to this). On the other hand, spinal cord patients may require more volume as they have significantly decreased tone. 75 mEq of Na+ and 40 mEq of K+ are required daily.


Clinical measures of volume are often inaccurate. Further, in neurosurgical patients a therapeutic trial may be necessary to optimize O2 delivery to the CNS (because the normal autoregulatory mechanisms often have failed).

In SAH patients in particular, hypovolemia probably occurs more than expected, and was originally thought to increase the risk of DIND [Neurosurgery 9: 514, 1981; J Neurosurg 55: 938, 1981; Neurosurgery 15: 354, 1984; Ann Neurol 18: 211, 1986]. At least two studies call this into question.

Studies Refuting the Relationship Between Volume and DIND

Neurol Res 28: 196, 2006

A study of 125 patients with SAH showed that 5.5% of 91 falls in a SBP (≥ 40 mm Hg) were followed by symptomatic vasospasm, whereas symptomatic vasospasm was observed in 69.2% of 52 patients a fall in SBP and in 43.8% of 73 patients without a fall in SBP (p<0.01, chi-squared test). A hypodense area on CT was observed in 48.1% of 52 patients with a fall in SBP in 28.8% of 73 patients without a fall in SBP (p<0.05). The authors concluded that falls in sBP might result from delayed cerebral vasospasm and/or brain dysfunction owing to SAH itself, and not vice versa [Neurol Res 28: 196, 2006]

Stroke 31:383, 2000

82 SAH patients at Columbia (post-op day < 7 s/p clipping) with no symptomatic vasospasm, were randomized to hypervolumemia (PA 14 mm Hg or CVP 8 mm Hg) vs. normovolumemia (PA 7 mm Hg or CVP 5 mm Hg), intervention with 250 mL of 5% albumin solution every 2 hours as needed. No difference in cerebral blood flow, fluid balance, or outcome [Stroke 31:383, 2000]

Cochrane Database Review

In fact, according to a Cochrane Database Review, the effects of volume expansion therapy have been studied properly in only two trials of patients with aneurysmal SAH, with very small numbers. At present, there is no sound evidence for the use of volume expansion therapy in patients with aneurysmal SAH [Cochrane Database Syst Rev. CD000483, 2004]

Volume Status in Subarachnoid Hemorrhage

  • Four early studies show that hypovolemia increases the risk of DIND following SAH
  • The data on therapeutic hypervolemia is less compelling. A RCT at Columbia showed no difference between CVP of 5 and CVP of 8 [Stroke 31:383, 2000]
  • The Cochrane Database Review does not endorse hypervolemic therapy for subarachnoid hemorrhage patients [Cochrane Database Syst Rev. CD000483, 2004]

Still, given that hypovolemia is a known risk factor for DIND and hypervolemia is known to cause increased side effects, placing a central line in all SAH patients and maintaining CVP 5-8 mm Hg seems reasonable. Monitoring should also be employed in patients on barbiturate therapy.

CPP vs. ICP for Goal-Directed Therapy

According to Andrews, a CPP of 60-70 mm Hg has not been scientifically validated. Furthermore, he claims that while many neurosurgeons are concerned that fluid overload can exacerbate ICP, there is no human data suggesting that this can happen. Retrospective studies suggest that as long as CPP > 60 mm Hg, keeping ICP < 20 mm Hg is more important than further increases in CPP [J Neurosurg 92: 1, 2000]. There appears to be no difference between CBF-targeted (CPP > 70 mm Hg and PaCO2 ~ 35 mm Hg) and ICP-targeted (CPP > 50 mm Hg and hyperventilation to a PaCO2 of 25-30 mm Hg) management protocols in terms of neurological outcomes [Crit Care Med 27: 2086, 1999] – the ICP-targeted approach is associated with increased cerebral infarction, and the CBF group is associated with increased ARDS.