How does mannitol decrease intracranial pressure?

How does mannitol decrease intracranial pressure?

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What is the mechanism by which mannitol is able to reduce intracranial pressure? Also why aren't other substances used for this purpose such as say sorbitol (an epimer) or in fact any other hyperosmotic agent?

Mannitol is a monosaccharide which is easy to produce and stable in solution. It is used clinically in doses ranging from 0.25 to 1.5 g/kg body weight. Solutions of 10% mannitol (osmolality 596 mOsm/kg) and 20% mannitol (osmolality 1,192 mOsm/kg) are commonly available for clinical use.

Cerebral effects

Mannitol does not cross the blood brain barrier so an elevated plasma osmolality due to a infusion of hypertonic mannitol is effective in removing fluid from the brain. This is called 'mannitol osmotherapy'. In the past other hypertonic solutions (eg hypertonic urea solution) have been used and currently in some places hypertonic glycerol solutions are available as an alternative to mannitol.

Mannitol infusions are useful to acutely decrease elevated intracranial pressure due to an intracranial space occupying lesion. A typical use would be in a patient with an intracerebral haematoma due to an acute traumatic head injury. The effect is rapid in onset (minutes) but only temporary (as the mannitol is excreted) but its use buys time for urgent definitive therapy (eg surgical evacuation of the haematoma and surgical haemostasis). A typical dose in an adult would be 0.5-1.5g/kg administered as the 20% solution.

Repeated doses of mannitol have less effect and as some slowly enters the brain, rebound intracranial hypertension is a risk. As the blood-brain barrier is probably disrupted in damaged areas of the brain, mannitol may be both less effective here and also more may enter the brain at these places. However, the therapeutic effect of mannitol is not dependent on a specific action at damaged areas of the brain but rather on a global effect in decreasing intracranial fluid volume and intracranial pressure so this has little relevance for a first dose of mannitol and especially if definitive surgical treatment is successful. Much more problematical is use of repeated doses of mannitol in ICU patients with traumatic intracranial hypertension in whom there is no surgically correctable cause such use is usually futile.

The brain cells also compensate for the presence of continued hypertonicity by the intracellular production of 'idiogenic osmoles'. The effect is to increase intracellular tonicity and allow brain cell volume to return towards normal presumably with improvement of intracellular functions despite the continued hypertonicity.

Use of mannitol infusions is common intraoperatively in some neurosurgical procedures. The aim is to decrease intracranial pressure and produce a 'slack brain' to facilitate surgical access.

Mannitol does not cross cell membranes so the cell volume of most other cells in the body is also decreased.

Renal effects

In the renal glomeruli, mannitol is freely filtered. It is not secreted or reabsorbed by the tubules. In the doses used clinically it retains water with it in the tubule and causes an 'osmotic diuresis'. Consequently, mannitol is classified as an 'osmotic diuretic'. The high flow of retained tubule fluid tends to have a flushing effect and washes fluid and solutes from the kidney. This effect is useful clinically in management of rhabdomyolysis. The aim is to 'wash' the myoglobin out of the tubules and prevent it precipitating there with obstruction and development of acute renal failure. The effect of mannitol for this use is aided by maintenance of adequate intravascular volume and by urinary alkalinisation (by administration of IV sodium bicarbonate).

Intravascular volume effects

Attention to intravascular volume status is important during any clinical use of mannitol. Initially, the tissue dehydrating effect will increase intravascular volume with the risk of precipitating volume overload and hypertension and/or acute congestive heart failure. Subsequently, the diuretic effect may result in hypovolaemia (and hypernatraemia). Frusemide (a loop diuretic) may be a useful adjunct in some cases to minimise the initial hypervolaemia.

Other effects

The increased intravascular water volume decreases the red cell concentration (decreased haematocrit) with a resultant decrease in blood viscosity. This may improve flow and oxygen delivery to some areas.

Mannitol has free radical scavenging properties and these may contribute to its therapeutic effects (though this has not so far been established).

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In: Veterinary Medicine , Vol. 94, No. 8, 08.1999, p. 717-724.

Research output : Contribution to journal › Article › peer-review

T1 - Using mannitol to treat traumatic brain injuries

N2 - Mannitol, which can decrease intracranial pressure, is often used to treat head injuries in people. But its use in veterinary medicine has been debated. This article reviews brain physiology and mannitol's efficacy in patients with traumatic brain injuries.

AB - Mannitol, which can decrease intracranial pressure, is often used to treat head injuries in people. But its use in veterinary medicine has been debated. This article reviews brain physiology and mannitol's efficacy in patients with traumatic brain injuries.

How does mannitol decrease intracranial pressure? - Biology

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A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial

Ankush Singla 1 , Preethy J Mathew 2 , Kiran Jangra 2 , Sunil K Gupta 3 , Shiv Lal Soni 2
1 Department of Anaesthesia, Adesh Medical College, Bhathinda, Punjab, India
2 Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication28-Feb-2020

Correspondence Address:
Kiran Jangra
Department of Anaesthesia and Intensive Care, 4th Floor, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.279671

Introduction: Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors.
Materials and Methods: A
prospective double-blind study was conducted on 30 patients randomized into two equal groups. Each patient was administered 5 ml/kg of either 20% mannitol or 3% HTS over 15 minutes (min) after skin incision. Hemodynamic data, brain relaxation and serum electrolyte levels were recorded.
Results: Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001).
Conclusions: Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.

Keywords: Brain, elevated intracranial pressure, hypertonic saline, mannitol, relaxation Key Messages: Both mannitol and hypertonic saline are equally efficacious in providing intraoperative relaxed brain in patients with the features of raised intracranial pressure. Mean arterial pressure and central venous pressure is better maintained with hypertonic saline.

How to cite this article:
Singla A, Mathew PJ, Jangra K, Gupta SK, Soni SL. A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial. Neurol India 202068:141-5

How to cite this URL:
Singla A, Mathew PJ, Jangra K, Gupta SK, Soni SL. A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial. Neurol India [serial online] 2020 [cited 2021 Jun 28]68:141-5. Available from:

Hypertonic saline (HTS) or mannitol are being routinely used to treat intracranial hypertension. [1],[2],[3],[4],[5] Mannitol acts through its osmotic diuretic properties that produce a reduction in brain water content and cerebrospinal fluid (CSF) pressure in approximately 20 min. [6] Besides this, it also reduces intracranial pressure (ICP) through the changes in blood fluid dynamics or blood rheology. Recently, HTS has appeared an appealing alternative to mannitol because its reflection coefficient is higher than that of mannitol (1.0 vs 0.9, respectively). Thus, HTS does not cross the intact blood–brain barrier. [7] Due to this property, HTS causes a greater increase in serum osmolality as compared to mannitol in equiomolar dosage. HTS creates a greater transendothelial osmotic gradient that results in more water movement from interstitial and intracellular brain to the intravascular space. HTS little diuretic effect and thus maintains hemodynamic stability and cerebral perfusion pressures. [8]

Previously published clinical trials comparing the effects of HTS and mannitol have included the patients with varied intracranial pathologies. The protocols of administration of HTS or mannitol and the osmolar load of the compounds were also variable. [7],[9],[10],[11],[12],[13] Wu et al. compared these two agents in elective supratentorial tumors for brain relaxation. They excluded the patents with signs of raised ICP. The authors found that brain relaxation was better in the HTS group than the mannitol group during elective supratentorial brain tumor surgery. Rozet et al. [7] also compared 20% mannitol and 3% HS for brain relaxation in patients scheduled to undergo craniotomy for varied neurosurgical pathologies and found that there was no difference in brain relaxation between two groups.

The present study was designed with the primary aim of comparing the effect of near equiosmolar equivolemic solutions of 3% HTS (1,024 mOsm/L) and 20% mannitol (1,098 mOsm/L) on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. The secondary aim was to compare the electrolyte changes after administering 3% HTS or 20% mannitol in these patients.

Patients were randomized using sealed envelopes into two groups group M, who received 20% mannitol (osmolarity = 1,098 mOsm/l) and group HTS, who received 3% HTS (osmolarity = 1,024 mOsm/l). Patients received 5 ml/kg of either drug for intraoperative brain relaxation. Drugs were loaded in the 50 cc syringes and labeled as the test drug. Both fluids were administered over 15 min using an infusion pump after skin incision via the central line. The anesthesiologist who recorded intraoperated data and the surgeon who assessed the brain relaxation were blinded to the drug being given.

Standard monitors were attached noninvasive blood pressure (NiBP), electrocardiography (ECG), pulse oximetry (SpO2), end tidal carbon dioxide concentration (EtCO2), and entropy. Anesthesia was induced with propofol and fentanyl, and vecuronium was used to facilitate intubation. Invasive arterial and central venous pressures (CVPs) were also monitored. Anesthesia was maintained using propofol and fentanyl infusion titrated to keep state entropy (SE) between 40 and 60. All patients were ventilated with oxygen-nitrous oxide mixture (50%:50%) to maintain arterial partial pressure of carbon dioxide (PaCO2) between 30 and 35 mm Hg.

Brain relaxation was scored by the surgeon and the anesthetist blinded to the test drug. A four-point scale was used by the surgeon: 1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm brain, 4 = bulging brain. [14] A second bolus of 5 ml/kg of the study drug was given if brain was not relaxed. A three-point scale was used by the anesthetist: = brain fully relaxed, fallen below both outer and inner tables of cranium, moving with respiration and pulsating with heartbeat, 2 = brain partially relaxed, lying between outer and inner tables of cranium, slight movement with respiration and slight pulsation with heartbeat, 3 = brain bulging out of the cranial cavity, no movement with respiration and no pulsation with heartbeat. We have used two scales to rule out the bias by the surgeon. The second scale was designed to include the brain characteristics and parameters, which are less amenable to the bias. The patients who had tight brain interfering the dura opening were managed with transient hyperventilation (EtCO2 up to 25 mm Hg) with optimum airway pressures, mild hypertension, additional dosages of hyperosmolar agent (100 ml mannitol/HTS).

Hemodynamic data and EtCO2 were recorded for comparisons initially at 5 min ( first 15 min after induction) and then at 15 min intervals till end of surgery. Arterial blood gases and electrolytes were measured before and 1 h after giving hypertonic agents. Serum sodium and potassium were measured at 24 and 48 h also. Hourly urine output was recorded.

Considering a significant difference of 1 point in brain relaxation score between the groups to be clinically significant, a power analysis based on 95% confidence interval and with power of 90% revealed a sample size of 30 subjects (15 subjects in each group).

The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 15.0 for Windows). The normality of the data was assessed by measures of skewness and Kolmogorov Smirnov tests of normality. The normally distributed data means were compared using t-test. For skewed data, the Mann-Whitney test was used. The Chi-square or Fisher's exact test was used to compare proportions, whichever was applicable. For time related variables, the Wilcoxon signed or paired t-test was applied. P ɘ.05 was considered significant. Multivariate analysis of variance (ANOVA) was applied for the comparison of hemodynamic and laboratory variables between the groups.

In our study, 20% mannitol and 3% HTS produced a similar effect on brain relaxation. There are various studies in the literature reporting varied results. Two previously published crossover, randomized trials demonstrated higher efficacy of HTS in decreasing ICPs than equimolar infusion of mannitol. [12],[13] The reported longer duration of ICP reduction after the use of HTS could be due to the combination of HTS with 6% hydroxyethyl starch solution [12] or with 6% dextran solution, [13] which are known to prolong the effects of HTS. Previous prospective mannitol and HTS during elective neurosurgery used different osmolar loads of the two agents and reported comparable brain relaxation between groups. [14],[15]

Rozet et al. [7] compared equiosmolar, equivolemic (5 ml/kg) loads of 20% mannitol and 3% HTS in different surgical setups supratentorial and infratentorial tumors, arteriovenous malformations, aneurysms, and subarachnoid hemorrhage. They found no difference in brain relaxation in those administered either mannitol or HTS. Here in this study, authors included a varied population and did not standardized the depth of anesthesia. Our study was conducted with similar dosages in patients with the features of raised ICP and found the similar results.

Recently, Ali et al. [16] had conducted a prospective, randomized, double-blind study in patients undergoing elective supratentorial surgeries. They compared received 5 ml/kg 20% mannitol or 3% HS as an infusion for 15 min. The authors monitored ICP using parenchymal monitor and also standardized the anesthesia by monitoring entropy. The authors concluded that 3% HS was more effective in ICP reduction than 20% mannitol during supratentorial tumor surgeries. However, the authors excluded the patients with raised ICP in their study.

In another study, Wu et al. [17] reported better brain relaxation with HTS during elective supratentorial brain tumor surgeries. The authors had used fixed volumes in their study 160 ml of 3% HTS or 150 ml of 20% mannitol. In addition, the depth of anesthesia was not monitored in these studies, which can affect brain relaxation. We have used a weight-based dosage of 5 ml/kg and entropy to keep the similar depth of anesthesia. This may account for the difference in results.

Dostal et al. [18] compared the infusion of 3.75 ml of equiosmolar concentrations of 3.2% HTS and 20% mannitol (osmolarity 1,099 each) and concluded that the HTS group has better brain relaxation than the mannitol group.

There was a small drop in MAP after induction in both groups. This may be due to the effect of various anesthetic agents. After 30 min, the MAP in the HTS group was maintained near baseline whereas MAP in the mannitol group was lower than baseline throughout the study period. HTS maintains MAP because of increases in cardiac output and intravascular volume. [19] HTS increases cardiac output due to its direct ionotropic effect, derived from improvement in cardiac microcirculation and contractility. [20] Volume expansion occurs because of hyperosmolarity that creates a gradient to move free water from the intracellular and interstitial compartments into the intravascular compartment. High urine output seen with mannitol might lead to the lower CVP. Compared with HTS, mannitol has a more prominent diuretic effect in all the 3 h of observation (P value ɘ.05). Hypernatremia after HTS was consistent with previous studies. [7],[16]

Both mannitol and HTS are equally efficacious in reducing the intracranial hypertension. MAP and CVP are better maintained close to the baseline with HTS. Thus, we advocate the use of HTS over mannitol for reducing the ICPs in patients with features of raised ICP undergoing supratentorial tumor resection. Administration of HTS is associated with a transient increase in serum sodium concentrations that is statistically significant but clinically insignificant and returns to normal within 48 h.

Hyperosmolar Therapy for Increased Intracranial Pressure (Review)

Acute brain injuries of all sorts increase the pressure inside the skull (intracranial pressure). Traumatic brain injury, bleeding in or around the brain, severe ischemic stroke, and acute hepatic failure all raise intracranial pressure, and increased intracranial pressure often becomes the most severe and immediate threat to life and long-term neurologic function in these conditions.

Hyperosmolar therapy with hypertonic saline or mannitol can rapidly reduce intracranial pressure, possibly saving lives and brain cells. In ideal circumstances, every patient with raised intracranial pressure would be treated at a center providing advanced neurologic critical care however, this is not the case in most of the world. Therefore, every intensivist should be at least familiar with the principles of hypertonic / hyperosmolar therapy for the treatment of acute increased intracranial pressure.

Pathophysiology of Increased Intracranial Pressure

Raised intracranial pressure (ICP) appears to be quite lethal: in traumatic brain injury patients, those with ICP > 40 mm Hg had a mortality of 56%, compared to 18% for those with ICP < 20 mm Hg. Most traumatic brain injuries causing long-term disability also initially presented with raised intracranial pressure.

As volume increases inside the skull, intracranial pressure exponentially rises after it passes an inflection point of

20-25 mm Hg. As ICP passes 50-60 mm Hg and approaches arterial pressure, global brain ischemia and eventual brain death result. The brain is 80% water, so using hyperosmolar agents to create an osmolar gradient between the inside of the brain and the systemic circulation has strong theoretical appeal. Hypertonic saline and mannitol are effective because they do not cross the blood-brain barrier (much), and thereby draw cerebrospinal fluid out of the cranium and fluid out of the injured brain, reducing pressure and further injury.

In brain injuries that include disruption of the blood-brain barrier, hyperosmolar therapy may be less effective.

There is no definitive evidence from prospective randomized trials that reducing intracranial pressure with hyperosmolar therapy saves lives or prevents disability. The theoretical evidence for its benefit is so persuasive, though, that placebo-controlled trials will not be performed. Post hoc analyses of randomized trials of brain injured patients, along with observational trials, suggest that reducing intracranial pressure does improve outcome.

Hypertonic Saline Vs. Mannitol: Dealer's Choice

There is no clear evidence of superiority of either mannitol or hypertonic saline at reducing intracranial pressure. One small trial suggested mannitol was better, others have favored hypertonic saline. The absolute differences of effects between agents have been quite small in these studies.

If a ventricular drain is placed, CSF can be removed and intracranial pressure can be measured directly this invasive approach carries a slight infection risk and has not been shown to improve outcomes.

If a direct-pressure monitoring device is not in place, the goal of hyperosmolar therapy is to either:

  • Increase the serum osmolarity initially to a target of 300-320 mOsm/L. Calculate osmolarity by (2 x Na) + (glucose / 18) + (BUN / 3), or use an osmolarity calculator, or your lab's true measured osmolality.
  • Increase serum sodium to 145-150 mmol/L.

Both these methods work whether using mannitol (an osmotic diuretic that causes generalized dehydration and hypernatremia) or hypertonic saline (which increases sodium concentration directly).

Mannitol sig: 20% mannitol bolus 0.25-1.0 grams / kg body weight q. 2-4 hours use higher doses in emergencies, lower doses for maintenance. Check osmolarity 20 minutes after infusion. If there is an osmolar gap between measured and calculated osmolarity, mannitol is still circulating wait and check again.

Hypertonic saline sig includes boluses of either:

  • 3% NaCl (513 mmol/L) bolus 150 ml
  • 7.5% NaCl (1283 mmol/L) bolus 75 ml
  • 23.4% NaCl (4008 mmol/L) bolus 30 ml

Use boluses don't use continuous infusions of 3%, the author advises it doesn't work as well.

Use the formula to determine the number of millimoles of sodium to infuse to achieve the 145-150 mmol/L serum Na goal:

sodium needed in mmol = (lean body weight in kg × 0.5 for a woman or 0.6 for a man) × (target sodium − current sodium in mmol/L).

Divide the result of this (# of mmol) by the concentration of your NaCl solution (in mmol/L) to get a total volume (L) to bolus in measured aliquots (see above).

Hypertonic saline greater than 3% concentration should be infused through a central line.

Adverse Effects of Hyperosmolar Therapy for Increased ICP

Mannitol can cause renal failure in high doses this seems to occur only when > 200 g of mannitol are given daily, from published reports. Dialysis / renal replacement therapy usually reverses the renal failure.

Mannitol can also cause a volume contraction alkalosis (metabolic alkalosis) with hypokalemia and hypochloremia. Providing normal saline infusion (0.9%) as a replacement fluid and maintaining euvolemic hypernatremia during therapy can prevent/treat this.

Hypertonic saline causes volume overload even when used properly, which can exacerbate congestive heart failure. Furosemide may be provided to reduce volume expansion. Hypertonic saline also can cause hypokalemia and hyperchloremia, as well as a mild metabolic acidosis.

Mannitol (and less often hypertonic saline) can cause a hyperglycemic, hyperosmolar state with encephalopathy, confusion, seizures, and focal neurologic signs. Diabetics and the elderly are more susceptible insulin should be given if this occurs, or for patients with unexplained seizures or rapidly rising glucose level, the author advises.

Hypertonic saline can cause skin sloughing if infused into the subcutaneous tissues through an infiltrated I.V. monitor I.V.s closely for patients receiving 3% peripherally and use a central line for higher concentrations.

Serum osmolarity of 320 mOsm/L has been traditionally considered the upper limit for safety, but some expert clinicians exceed this in practice and have not reported any safety problems, according to the author.

Increased Intracranial Pressure: Other Things to Consider

Surgical evacuation of subdural hematoma can be highly effective, but for more diffuse processes (brain contusion, cerebral edema, etc), surgery has not been shown to be superior than medical management.

Avoid serum hypo-osmolarity by not infusing anything with lower osmolarity than 0.9% NaCl normal saline -- no lactated Ringer's, D-5-W, half-normal saline, etc.

Hyperventilation is worthwhile as a bridge to other therapies, but its reductions in ICP through cerebral vasoconstriction last less than an hour.

External ventricular drains can reduce ICP quickly, but their effects may also be short-lived (limited to how much CSF is in the ventricles).

Glucocorticoids reduce edema surrounding brain masses, but don't reduce intracranial pressure in other situations.

Induced hypothermia reduces intracranial pressure initially, but can cause cerebral edema during rewarming, and is not advisable as a treatment for raised ICP (except possibly for another purpose, such as post-cardiac arrest).

Ropper AH. Hyperosmolar Therapy for Raised Intracranial Pressure. NEJM 2012367:746-752.

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Intracranial pressure monitoring

Clinical symptoms of increased ICP, such as headache, nausea, and vomiting, are impossible to elicit in comatose patients. Papilledema is a reliable sign of intracranial hypertension, but is uncommon after head injury, even in patients with documented elevated ICP. In a study of patients with head trauma, 54% of patients had increased ICP, but only 3.5% had papilledema on fundoscopic examination [18]. Other signs, such as pupillary dilation and decerebrate posturing, can occur in the absence of intracranial hypertension. CT scan signs of brain swelling, such as midline shift and compressed basal cisterns, are predictive of increased ICP, but intracranial hypertension can occur without those findings [19].

Types of monitors

The ventriculostomy catheter is the preferred device for monitoring ICP and the standard against which all newer monitors are compared [20]. An intraventricular catheter is connected to an external pressure transducer via fluid-filled tubing. The advantages of the ventriculostomy are its relatively low cost, the option to use it for therapeutic CSF drainage, and its ability to recalibrate to minimize errors owing to measurement drift. The disadvantages are difficulties with insertion into compressed or displaced ventricles, inaccuracies of the pressure measurements because of obstruction of the fluid column, and the need to maintain the transducer at a fixed reference point relative to the patient’s head. The system should be checked for proper functioning at least every 2 to 4 hours, and any time there is a change in the ICP, neurologic examination, and CSF output. This check should include assessing for the presence of an adequate waveform, which should have respiratory variations and transmitted pulse pressure.

When the ventricle cannot be cannulated, other alternatives can be used. Different non𠄿luid-coupled devices are available for ICP monitoring and have replaced the subarachnoid bolt. The microsensor transducer and the fiberoptic transducer are the most widely available. These transducer-tipped catheters can be inserted in the subdural space or directly into the brain tissue [21]. The main advantages of these monitors is the ease of insertion, especially in patients with compressed ventricles however, none of the transducer-tipped catheters can be reset to zero after they are inserted into the skull, and they exhibit measurement drift over time [22]. Subdural and epidural monitors for ICP measurements are less accurate compared to ventriculostomy or parenchymal monitors.

For surgical patients, the ICP monitor may be inserted at the end of the surgical procedure. ICP monitoring is continued for as long as treatment of intracranial hypertension is required, typically 3 to 5 days. A secondary increase in ICP may be observed 3 to 10 days after trauma in 30% of patients with intracranial hypertension [16] secondary to development of delayed intracerebral hematoma, cerebral vasospasm, or systemic factors such as hypoxia and hypotension.

Types of intracranial pressure waveforms

The variations seen in the normal tracing of ICP originate from small pulsations transmitted from the systemic blood pressure to the intracranial cavity. These blood pressure pulsations are superimposed on slower oscillation caused by the respiratory cycle. In mechanically ventilated patients, the pressure in the superior vena cava increases during inspiration, which reduces venous outflow from the cranium, causing an elevation in ICP.

Pathologic waveforms

As the ICP increases, cerebral compliance decreases, arterial pulses become more pronounced, and venous components disappear. Pathologic waveforms include Lundberg A, B, and C types. Lundberg A waves or plateau waves are ICP elevations to more than 50 mm Hg lasting 5 to 20 minutes. These waves are accompanied by a simultaneous increase in MAP, but it is not clearly understood if the change in MAP is cause or effect. Lundberg B waves or pressure pulses have an amplitude of 50 mm Hg and occur every 30 seconds to 2 minutes. Lundberg C waves have an amplitude of 20 mm Hg and a frequency of 4 to 8 per minute they are seen in the normal ICP waveform, but high-amplitude C waves may be superimposed on plateau waves [23].

Indications for intracranial pressure monitoring

Monitoring of ICP is an invasive technique and has some associated risks. For a favorable risk-to-benefit ratio, ICP monitoring is indicated only in patients with significant risk of intracranial hypertension [12] (Box 2). Patients with TBI who are particularly at risk for developing an elevated ICP include those with Glasgow Coma Scale of 8 or less after cardiopulmonary resuscitation and who have an abnormal admission head CT scan. Such abnormalities might include low-density or high-density lesions, including contusions epidural, subdural, or intraparenchymal hematomas compression of basal cisterns and edema [24]. Patients who are able to follow commands have a low risk for developing intracranial hypertension, and serial neurologic examinations can be followed.

Box 2: Indications for ICP Monitoring

GCS Score: 3𠄸 (after resuscitation)

Abnormal Admission Head CT Scan

Compressed basal cisterns

Normal Admission Head CT Scan PLUS 2 or more of the following

Systolic blood pressure < 90 mm Hg

Although CT scan findings are not accurate in determining the actual ICP, the risk of developing intracranial hypertension can be predicted. Sixty percent of patients with closed head injury and an abnormal CT scan have intracranial hypertension. Only 13% of patients with a normal CT scan have elevated ICP except for patients with certain risk factors, including age greater than 40 years old, systolic blood pressure less than 90 mm Hg, and decerebrate or decorticate posturing on motor examination. Patients with a normal CT scan have 60% risk of intracranial hypertension if they have two risk factors and 4% if they have only one risk factor. Patients with a Glasgow Coma Scale score greater than 8 also might be considered for ICP monitoring if they require treatment that would not allow serial neurologic examinations, such as prolonged anesthesia for surgery of multiple injuries or prolonged pharmacologic paralysis for ventilatory management, or if they require a treatment that might increase ICP, such as positive end-expiratory pressure (PEEP). Other, less common indications include patients with multiple systemic injuries with altered level of consciousness and subsequent to removal of an intracranial mass (eg, hematoma, tumor) [12]. ICP monitoring also must be considered in nontraumatic conditions in which an intracranial mass lesion is present (eg, cerebral infarction, spontaneous intracerebral hemorrhage) and has a likelihood of expansion leading to intracranial hypertension and clinical deterioration. The duration of monitoring is until ICP has been normal for 24 to 48 hours without ICP therapy.

Complications of intracranial pressure monitoring

The most common complication of ventriculostomy catheter placement is infection with an incidence of 5% to 14% colonization of the device is more common than clinical infection [25]. A study found no significant reduction in infection rate in patients undergoing prophylactic change of monitors before day 5, compared with those whose catheters were in place for 5 days or more.[26]. Factors that are not associated with infection are insertion of the catheter in the neurologic ICU, previous catheter insertion, drainage of CSF, and use of steroids. In a group of patients with prolonged ventricular drainage of 10 days or more, a non-linear increase in daily infection rate was observed over the initial 4 days but remained constant despite prolonged catheter use [27]. Use of antibiotic-coated ventriculostomy catheters has been shown to reduce the risk of infection from 9.4% to 1.3% [28]. Other complications of ventriculostomy catheters are hemorrhage with an overall incidence of 1.4%, malfunction, obstruction, and malposition.


A total of 108 rats were subjected to fluid percussion injury or served as controls. Twelve injured animals died before the end of the experiment. Protocol errors or errors in tissue handling or blood sampling occurred in 5 animals, leaving 91 animals for which osmolality and brain water data were available.

Blood pressure, blood gases, osmolality, and hemispheric brain water content data for all groups are presented in table 1.

Injury resulted in an increase in water content in both hemispheres (control vs. impact only), although water content was always greater in the left hemisphere (paired t test within each group, P = 0.02–0.0001).

As expected, mannitol resulted in a dose-related increase in osmolality (P < 0.0001, analysis of variance containing all four mannitol doses plus impact only). Similarly, there was a dose-related decrease in brain water content (both hemispheres, P < 0.0001).

There were no differences in pH, arterial blood gas values, plasma osmolality, or MAP before drug treatment in the four selected groups. Statistically significant reductions in MAP and pH (both vs. baseline within the groups and vs. impact-only animals) were seen in the 8 g/kg mannitol and 8 g/kg mannitol plus 8 mg/kg furosemide groups. There were significant increases in plasma osmolality in both of the groups given 8 g/kg mannitol (both vs. baseline measurements within the group and vs. impact-only animals). Furosemide alone did not alter plasma osmolality or brain water content (vs. impact only). Both 8 g/kg mannitol and the combination of 8 g/kg mannitol plus 8 mg/kg furosemide resulted in a significant decrease in water content versus impact only (both hemispheres). There were, however, no differences in osmolality or brain water content between these latter two groups. These results are summarized in figure 1.

Fig. 1. Water content (% water) for the lesioned left hemisphere ( top) and osmolality ( bottom) for the four groups used in the primary analysis. All values are mean ± SD. Mannitol, 8 g/kg, and the combination of 8 g/kg mannitol plus 8 mg/kg furosemide significantly reduced water content and increased osmolality as compared with impact-only animals and versus8 mg/kg furosemide alone (which did not differ from impact only). However, there was no difference between mannitol and mannitol-plus-furosemide groups (in either water content or osmolality).

Fig. 1. Water content (% water) for the lesioned left hemisphere ( top) and osmolality ( bottom) for the four groups used in the primary analysis. All values are mean ± SD. Mannitol, 8 g/kg, and the combination of 8 g/kg mannitol plus 8 mg/kg furosemide significantly reduced water content and increased osmolality as compared with impact-only animals and versus8 mg/kg furosemide alone (which did not differ from impact only). However, there was no difference between mannitol and mannitol-plus-furosemide groups (in either water content or osmolality).


Osmotic diuretics have their major effect in the proximal convoluted tubule and the descending limb of the Loop of Henle. These sites are freely permeable to water. Through osmotic effects, they also oppose the action of ADH in the collecting tubule. The presence of a nonreabsorbable solute such as mannitol prevents the normal absorption of water by interposing a countervailing osmotic force. As a result, urine volume increases.

The increase in urine flow rate decreases the contact time between fluid and the tubular epithelium, thus reducing sodium as well as water reabsorption. The resulting natriuresis is of lesser magnitude than the water diuresis, leading eventually to excessive water loss and hypernatremia.

Any osmotically active agent that is filtered by the glomerulus but not reabsorbed causes water to be retained in these segments and promotes a water diuresis. Such agents can be used to reduce intracranial pressure and to promote prompt removal of renal toxins. The prototypical osmotic diuretic is mannitol. [5]

Mannitol lowers the intra cranial pressure through two effects in the brain. The first, rheological effect, reduces blood viscosity, and promotes plasma expansion and cerebral oxygen delivery. In response, cerebral vasoconstriction occurs due to autoregulation, and cerebral blood volume is decreased. The second effect occurs through creation of an osmotic gradient across the blood-brain barrier, leading to the movement of water from the parenchyma to the intravascular space. Brain tissue volume is decreased and, therefore, ICP is lowered. [6] [7]

  1. ^ "osmotic diuretic" at Dorland's Medical Dictionary
  2. ^"Mannitol" . Retrieved 2008-12-20 .
  3. ^
  4. Trevor, Anthony J. Katzung, Bertram G. (2003). Pharmacology. New York: Lange Medical Books/McGraw-Hill, Medical Publishing Division. p. 46. ISBN0-07-139930-5 .
  5. ^
  6. Sakowitz OW, Stover JF, Sarrafzadeh AS, Unterberg AW, Kiening KL (February 2007). "Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients". J Trauma. 62 (2): 292–8. doi:10.1097/01.ta.0000203560.03937.2d. PMID17297315.
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  8. Brunton, Laurence (2011). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (12th ed.). The McGraw-Hill Companies, Inc. pp. Chapter 25.
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  10. Messeter, Kenneth Nordström, Carl-Henrik Sundbärg, Göran Algotsson, Lars Ryding, Erik (February 1986). "Cerebral hemodynamics in patients with acute severe head trauma". Journal of Neurosurgery. 64 (2): 231–237. doi:10.3171/jns.1986.64.2.0231. ISSN0022-3085. PMID3080555.
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  12. James, H. E. (September 1980). "Methodology for the control of intracranial pressure with hypertonic mannitol". Acta Neurochirurgica. 51 (3–4): 161–172. doi:10.1007/bf01406742. ISSN0001-6268. PMID6768226. S2CID40808775.

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Medical uses Edit

In the United States, mannitol is indicated for the reduction of intracranial pressure and treatment of cerebral edema and elevated intraocular pressure. [1]

In the European Union, mannitol is indicated for the treatment of cystic fibrosis (CF) in adults aged 18 years and above as an add-on therapy to best standard of care. [2]

Mannitol is used intravenously to reduce acutely raised intracranial pressure until more definitive treatment can be applied, [12] e.g., after head trauma. Intra-arterial infusions of mannitol can transiently open the blood-brain barrier by disrupting tight junctions. [13] [14]

It may also be used for certain cases of kidney failure with low urine output, decreasing pressure in the eye, to increase the elimination of certain toxins, and to treat fluid build up. [6]

Intraoperative mannitol prior to vessel clamp release during renal transplant has been shown to reduce post-transplant kidney injury, but has not been shown to reduce graft rejection. [ medical citation needed ]

Mannitol acts as an osmotic laxative [1] [15] in oral doses larger than 20 g, [16] and is sometimes sold as a laxative for children. [ citation needed ]

The use of mannitol, when inhaled, as a bronchial irritant as an alternative method of diagnosis of exercise-induced asthma has been proposed. A 2013 systematic review concluded evidence to support its use for this purpose at this time is insufficient. [17]

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass. The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage.

Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it passes through the venous system. Because the mannitol dissolves readily in blood, the sharp point becomes exposed at its destination.

Mannitol is also the first drug of choice to treat acute glaucoma in veterinary medicine. It is administered as a 20% solution intravenously. It dehydrates the vitreous humor and, therefore, lowers the intraocular pressure. However, it requires an intact blood-ocular barrier to work. [18]

Food Edit

Mannitol increases blood glucose to a lesser extent than sucrose (thus having a relatively low glycemic index [19] ) so is used as a sweetener for people with diabetes, and in chewing gums. Although mannitol has a higher heat of solution than most sugar alcohols, its comparatively low solubility reduces the cooling effect usually found in mint candies and gums. However, when mannitol is completely dissolved in a product, it induces a strong cooling effect. [20] Also, it has a very low hygroscopicity – it does not pick up water from the air until the humidity level is 98%. This makes mannitol very useful as a coating for hard candies, dried fruits, and chewing gums, and it is often included as an ingredient in candies and chewing gum. [21] The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets. [22]

Analytical chemistry Edit

Mannitol can be used to form a complex with boric acid. This increases the acid strength of the boric acid, permitting better precision in volumetric analysis of this acid. [23]

Other Edit

Mannitol is the primary ingredient of mannitol salt agar, a bacterial growth medium, and is used in others.

Mannitol is used as a cutting agent [24] in various drugs that are used intranasally (snorted), such as cocaine. A mixture of mannitol and fentanyl (or fentanyl analogs) in ratio 1:10 is labeled and sold as "China white", a popular heroin substitute. [ citation needed ]

Mannitol is contraindicated in people with anuria, severe hypovolemia, pre-existing severe pulmonary vascular congestion or pulmonary edema, and active intracranial bleeding except during craniotomy. [1]

Adverse effects include hyponatremia and volume depletion leading to metabolic acidosis. [7]

Mannitol is an isomer of sorbitol, another sugar alcohol the two differ only in the orientation of the hydroxyl group on carbon 2. [25] While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.

Mannitol is classified as a sugar alcohol that is, it can be derived from a sugar (mannose) by reduction. Other sugar alcohols include xylitol and sorbitol. Mannitol and sorbitol are isomers, the only difference being the orientation of the hydroxyl group on carbon 2. [20]

Industrial synthesis Edit

Mannitol is commonly produced via the hydrogenation of fructose, which is formed from either starch or sucrose (common table sugar). Although starch is a cheaper source than sucrose, the transformation of starch is much more complicated. Eventually, it yields a syrup containing about 42% fructose, 52% glucose, and 6% maltose. Sucrose is simply hydrolyzed into an invert sugar syrup, which contains about 50% fructose. In both cases, the syrups are chromatographically purified to contain 90–95% fructose. The fructose is then hydrogenated over a nickel catalyst into a mixture of isomers sorbitol and mannitol. Yield is typically 50%:50%, although slightly alkaline reaction conditions can slightly increase mannitol yields. [20]

Biosyntheses Edit

Mannitol is one of the most abundant energy and carbon storage molecules in nature, produced by a plethora of organisms, including bacteria, yeasts, fungi, algae, lichens, and many plants. [26] Fermentation by microorganisms is an alternative to the traditional industrial synthesis. A fructose to mannitol metabolic pathway, known as the mannitol cycle in fungi, has been discovered in a type of red algae (Caloglossa leprieurii), and it is highly possible that other microorganisms employ similar such pathways. [27] A class of lactic acid bacteria, labeled heterofermentive because of their multiple fermentation pathways, convert either three fructose molecules or two fructose and one glucose molecule into two mannitol molecules, and one molecule each of lactic acid, acetic acid, and carbon dioxide. Feedstock syrups containing medium to large concentrations of fructose (for example, cashew apple juice, containing 55% fructose: 45% glucose) can produce yields 200 g (7.1 oz) mannitol per liter of feedstock. Further research is being conducted, studying ways to engineer even more efficient mannitol pathways in lactic acid bacteria, as well as the use of other microorganisms such as yeast [26] and E. coli in mannitol production. When food-grade strains of any of the aforementioned microorganisms are used, the mannitol and the organism itself are directly applicable to food products, avoiding the need for careful separation of microorganism and mannitol crystals. Although this is a promising method, steps are needed to scale it up to industrially needed quantities. [27]

Natural extraction Edit

Since mannitol is found in a wide variety of natural products, including almost all plants, it can be directly extracted from natural products, rather than chemical or biological syntheses. In fact, in China, isolation from seaweed is the most common form of mannitol production. [21] Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree. It is a constituent of saw palmetto (Serenoa). [28]

Traditionally, mannitol is extracted by the Soxhlet extraction, using ethanol, water, and methanol to steam and then hydrolysis of the crude material. The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product. Another method of extraction is using supercritical and subcritical fluids. These fluids are at such a stage that no difference exists between the liquid and gas stages, so are more diffusive than normal fluids. This is considered to make them much more effective mass transfer agents than normal liquids. The super- or subcritical fluid is pumped through the natural product, and the mostly mannitol product is easily separated from the solvent and minute amount of byproduct.

Supercritical carbon dioxide extraction of olive leaves has been shown to require less solvent per measure of leaf than a traditional extraction — 141.7 g (5.00 oz) CO2 versus 194.4 g (6.86 oz) ethanol per 1 g (0.035 oz) olive leaf. Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction. It requires only 4.01 g (0.141 oz) water per 1 g (0.035 oz) of olive leaf, and gives a yield of 76.75% mannitol. Both super- and subcritical extractions are cheaper, faster, purer, and more environmentally friendly than the traditional extraction. However, the required high operating temperatures and pressures are causes for hesitancy in the industrial use of this technique. [27]

Julije Domac elucidated the structure of hexene and mannitol obtained from Caspian manna. He determined the place of the double bond in hexene obtained from mannitol and proved that it is a derivative of a normal hexene. This also solved the structure of mannitol, which was unknown until then. [29] [30] [31] [32]

The three studies [33] [34] [35] that initially found that high-dose mannitol was effective in cases of severe head injury were the subject of an investigation published in 2007. [36] Although several authors are listed with Dr. Julio Cruz, it is unclear whether the authors had knowledge of how the patients were recruited. Further, the Federal University of São Paulo, which Dr. Cruz gave as his affiliation, has never employed him. As a result of doubt surrounding Cruz's work, an updated version of the Cochrane review excludes all studies by Julio Cruz, leaving only 4 studies. [5] Due to differences in selection of control groups, a conclusion about the clinical use of mannitol could not be reached.

Approach to head trauma (Proceedings)

The treatment of head trauma is a controversial topic in veterinary medicine. Unfortunately, there does not appear to be a generalized consensus as to the approach to treating head trauma. In general, most veterinarians will agree that the main goal of treating head trauma is to the restore oxygen delivery to the brain and to reduce cerebral edema and intracranial pressure. The controversial part is how to achieve these goals. The only treatments in head trauma that appear to be agreed upon are treatment of shock, oxygen therapy, and head elevation.

During head trauma, pathophysiologically there is primary brain injury and secondary brain injury. Primary brain injury is the injury that occurs at the time of the trauma. This includes the direct injury to the parenchyma and blood vessels in the brain. There generally is nothing that can be done to help the primary injury except for tincture of time. Secondary brain injury is the injury that occurs as a result of inflammation, edema, vasculitis, and increased intracranial pressure. Depletion of ATP in the brain (which is exacerbated by hypoxemia and hypovolemia), increased release of excitatory neurotransmitters (especially glutamate), hyperglycemia, and oxygen free radicals in the brain all contribute to secondary brain injury. It is the secondary brain injury that can be helped with appropriate treatment.

The first step is to normalize blood pressure. In order to maximize oxygen delivery to the brain, cerebral perfusion pressure needs to be maintained. Cerebral perfusion pressure (CPP) is a reflection of mean arterial pressure (MAP) minus intracranial pressure (ICP). If the patient is in shock and is hypotensive, the animal's blood pressure needs to be normalized in order to maintain CPP and hence oxygen delivery to the brain. Normalizing the mean arterial pressure also decreases ICP, since low blood pressure causes cerebral vasodilation therefore, normalizing the blood pressure will aid in reversal of cerebral vasodilation. In addition, the normal cerebral vasculature autoregulation that occurs with changes in blood pressure is frequently ineffective in the low blood pressure ranges in the head trauma patient. Since the cranial vault tends to be a finite space and the main structures in the cranial vault are parenchyma, blood vessels, and CSF, attempts to prevent cerebral vasodilation are necessary, especially if there is presence of cerebral edema or hemorrhage, which is competing for space in the cranial vault. In addition to normalizing blood pressure, maintaining a normal arterial partial pressure of carbon dioxide is also important, as hypercarbia will cause cerebral vasodilation. Avoiding anesthesia or excessive sedation will help prevent hypoventilation. Buprenorphine or butorphanol may be better analgesic choices than pure opioids (i.e. morphine, hydromorphone) if hypoventilation is of concern.

The concept of normalizing blood pressure leads to the controversial subject of which fluid resuscitation is best for head trauma patients. In other words, which fluid will raise blood pressure quickly, but will not contribute significantly to secondary brain injury and edema? In general, if the amount of crystalloids that are administered can be reduced, it will decrease the progression of cerebral edema. Hetastarch alone as a resuscitation fluid (5-10 ml/kg IV bolus over 10-15 minutes), or a combination of hetastarch/hypertonic saline or dextrans/hypertonic saline (3-5 mls/kg IV bolus over 10-15 minutes of a combination of 2/3 colloid and 1/3 21% hypertonic saline) is currently thought to be the best resuscitation fluid to reduce secondary brain injury in head trauma. In fact, the mere use of colloids, regardless of the amount of crystalloids given, has been shown to be beneficial in head trauma. Crystalloids can still be used judiciously and should not be withheld in the shock patient if colloids are not immediately available (starting with a ¼ shock dose over 10-15 minutes is generally safe, as long as the fluid is titrated to effect – the ¼ shock dose is approximately 15 ml/kg IV in the cat and 22 ml/kg IV in the dog). There is some evidence that in neonates, Lactated Ringers is the best crystalloid choice because neonates utilize lactate more efficiently as an energy source in the brain compared with glucose. It is important to note that hypertonic saline alone has not been shown to be helpful in head trauma patients and in fact may worsen outcome. Targeting a MAP of 80 mmHg should be the resuscitation goal.

Once the animal is properly resuscitated for shock, then the second step is to attempt to decrease intracranial pressure. As previously discussed, normalizing MAP will help decrease ICP by decreasing cerebral vasodilation. Secondly, oxygen supplementation may decrease ICP because during hypoxemia the brain vasculature vasodilates in an attempt to maintain oxygen delivery to the brain. The third treatment of choice for elevated ICP is 15 to 30 degree head elevation. This will help to decrease intracranial pressure by potentially decreasing intracranial blood volume. In addition, avoiding pressure on the jugular veins and avoiding making the animal cough (an important thing to keep in mind if you have to intubate the animal) will help prevent unnecessary increases in ICP.

The fourth treatment of choice for elevated ICP is mannitol administration. Administering mannitol to the head trauma patient is controversial. Mannitol is an osmotic diuretic, which in theory will decrease blood volume and can decrease cerebral edema. In addition, it is a free-radical scavenger and will decrease blood viscosity which may help with micro-perfusion. The argument against mannitol is that if there is an active bleed in the brain, it could leak out with the hemorrhage, causing a hyperosmolar environment and potentially pull more fluid into the area of hemorrhage. Another argument against mannitol use is that it can transiently cause increased intravascular volume, which could transiently increase intracranial pressure. Despite concerns over mannitol use, in the author's experience, it seems that the majority of head trauma cases in veterinary medicine respond favorably to mannitol and rarely decline after mannitol use. This may be because subdural hematomas appear to be fairly uncommon in veterinary patients, although this may simply be a reflection of the fact that we advanced imaging (i.e. CT) to diagnose intracranial bleeding is rarely performed in these patients. Giving 0.5 to 1 g/kg of mannitol IV over 20-30 minutes is generally the protocol. If there is concern about intracranial hemorrhage, giving 0.5 g/kg initially and then observing for improvement or decline in mental status may be useful. If the signs improve or remain unchanged after the 0.5 g/kg, then the dose can be repeated. Do not exceed 3 g/kg total dose in a 24 hours time period.

Lasix therapy has been advocated for use to decrease intracranial pressure in conjunction with mannitol therapy. Some neurologists feel that lasix in addition to mannitol enhances the diuretic effect and more significantly reduces ICP. There appears to be controversy as to when the lasix should be administered (either 15-20 minutes prior to or after the mannitol). The dose is typically 1-2 mg/kg IV.

Steroid use in head trauma remains controversial, but currently is out of favor in the emergency and critical care specialty. Steroids have not been shown to improve outcome and have worsened outcome in some human studies. There is no clear-cut reason for the worse outcome with steroid use, but it may be associated with hyperglycemia (see below). The only time steroids in head trauma have been shown to be helpful is PRIOR to the head trauma incident!

Hyperglycemia in head trauma has become a hot topic. In people, the degree of hyperglycemia on presentation is associated with the severity of the head trauma and outcome. A study in dogs and cats by Dr. Rebecca Syring out of the University of Pennsylvania confirmed that hyperglycemia correlates with the severity of head trauma, but is not correlated with outcome. It is unclear why hyperglycemia is present in severe head trauma, although the leading theory is that the amount of catecholamine release (and hence the severity of trauma) is associated with the severity of hyperglycemia. It is also unclear whether or not the hyperglycemia in and of itself contributes to secondary brain injury and cerebral edema. Some people believe the hyperglycemia may be detrimental if brain oxygen delivery is reduced. This is because glucose metabolism in the brain during anaerobic metabolism will potentially increase brain lactate levels, which may lead to cellular acidosis and increased brain cell death. To date, there is not data as to whether veterinarians should be controlling hyperglycemia associated with head trauma or not.

Future considerations for treatment of secondary head trauma may eventually focus on attempting to decrease brain cell death by controlling glutamate levels in the brain and decreasing calcium build up in the cells. This may be achieved by blocking NMDA receptors, which release glutamate, and by administering calcium channel blockers. There have been no studies to date regarding these techniques and currently cannot be recommended clinically.

Once the head trauma patient is stabilized, the animal must be continually reassessed neurologically. Neurologic status is extremely difficult to assess in a patient that is in shock, as the shock state in and of itself may cause decreased mentation. In general, animals appear to recover very quickly from head trauma. It is the author's recommendation to at least give head trauma patients 24-48 hours of time before making a final decision as to which direction a patient may go regarding recovery. However, a patient that is comatose for >48 hours likely has a grave prognosis. Keep in mind that some neurologic injuries take months to fully recover. The nice thing about the veterinary patient is that higher cognitive function is not necessary to function on a daily basis. If the animal can eat, drink, eliminate, interact appropriately, and sleep, and an owner is willing to nurse the animal along, time may be all that is needed to make a full recovery with minimal residual side effects. In fact, many head trauma patients will continue eating and drinking despite being in an obtunded state (i.e. depressed mentation with a decreased response to stimuli and environment). It is clearly important to ensure that the animal has a gag reflex prior to offering food or water.

The Modified Glasgow Coma Scale may help determine prognosis. A score of 3-8 is considered Grave, 9-14 is considered guarded, and 15-18 is considered to be good.

In conclusion, head trauma is treated somewhat differently than other types of traumatic injuries. Focusing on maintaining mean arterial pressure, volume resuscitation with colloids, reducing intracranial pressure, providing oxygen for 12-24 hours, elevating the head, and tincture of time are all important concepts in treating head trauma. Making decisions about neurologic status too early may result in inappropriate assessment of long term prognosis. Many animals do remarkably well after head trauma and should be given the opportunity to recover for a period of time prior to making an ultimate prognosis as to recovery.

References/suggested reading

Dewey CW. Brain Trauma. In: Wingfield WE, Raffe MR, editors. The Veterinary ICU Book. Jackson Hole, WY: Teton New Media Press 2002. pp. 911-920.

Dewey CW, Emergency Treatment of Head/Spinal Trauma, 11th Annual IVECCS Proc., 2005, pp 493-497.

Syring, R. S. Hyperglycemia in dogs and cats with head trauma: 122 cases (1997-1999). Journal of the American Veterinary Medical Association 218 (7), 2001, p.1124-1129.

McMichael, M. and Dhupa, N. Pediatric critical care medicine: physiologic considerations. Compendium on Continuing Education for the Practicing Veterinarian 22(3), 2000, p.206-215.

McMichael, M. and Dhupa, N. Pediatric critical care medicine: specific syndromes. Compendium on Continuing Education for the Practicing Veterinarian 22(4), 2000, p.353-360.

Platt, S.R., Radaelli S.T., and McDonnell J.J. The prognostic value of the modified Glasgow Coma Scale in head trauma in dogs. Journal of Veterinary Internal Medicine 15(6), 2001, p. 581-584.

Matthews KA. Veterinary emergency and Critical Care Manual – Suggested Reading.

Diabetes and Kidney Disease

In the United States diabetes is the most common cause of kidney failure. High blood pressure and high levels of blood glucose increase the risk that a person with diabetes will eventually progress to kidney failure. Kidney disease in people with diabetes develops over the course of many years. albumin and eGFR are two key markers for kidney disease in people with diabetes. Controlling high blood pressure, blood pressure medications, a moderate protein diet, and compliant management of blood glucose can slow the progression of kidney disease. For those patients who's kidneys eventually fail, dialysis or kidney transplantation is the only option.