A 74-year old male presents with sudden onset of ‘dizziness’ while doing minor chores in his backyard 30 minutes prior. He develops slurred speech and right sided facial paralysis and right sided facial droop.
His past medical history includes hypertension and dyslipidemia. Medications include ramipril and atorvastatin.
He is brought to the local community hospital. His initial vitals are T 37.0 HR 94, BP 198/100, RR 20, 98% room air. Pupils are equal and reactive. He is found to be aphasic. While his eyes are open spontaneously, he will not track. He obeys simple commands on the left side only intermittently. He has a dense paralysis on the right. Cardiorespiratory exam is unremarkable.
The sending hospital does not have a CT scanner available. A transport is requested to the local tertiary centre.
What is your initial differential diagnosis?
The main differential diagnosis to consider here is a left hemispheric stroke, most likely ischemic though hemorrhage is always a possibility. The dizziness suggests the possibility of posterior fossa involvement. Without a history of seizure, post-ictal paresis (i.e. Todd’s Paralysis) is unlikely. Acapillary glucose must be expedited to exclude hypoglycemia. The acuity of this patient’s presentation makes an acute presentation of an intracranial tumour or abscess even less likely. In short, this patient needs a non-contrast CT head and capillary glucose as soon as possible.
100 minutes post symptom onset the transport team arrives in your hospital. The patient’s heart rate is fluctuating between 70-80 bpm (sinus arrhythmia), though there have been 2 episodes of bradycardia down to 30 bpm (rhythm uncertain). The patient’s blood pressure on arrival is 222/104. GCS is 11 (E = 3, V = 3, M = 5). Capillary glucose is 6 mmol/L.
You suspect the patient may have elevated intracranial pressure (ICP). How could you confirm this?
Only because a CT scan is not readily available, you can consider using point of care ultrasound. This is to assess for optic nerve sheath diameter (ONSD) – the ultrasonographic equivalent of papilledema. You use a linear probe and measure the ONSD 3 mm posterior to the globe. While there is debate about the numbers to use, a diameter >5mm is approximately 90% sensitive and 80% specific. Less than 5 mm is generally assumed normal. An ONSD >6mm almost certainly abnormal. Of note, this is a dynamic marker of ICP as the ONSD typically decreases following interventions that decrease ICP.
Great post on use of POCUS to detect elevated intracranial pressure at Sinai EM Ultrasound
What are your initial steps in management?
This patient is demonstrating Cushing’s Triad – irregular respirations, hypertension and reflex bradycardia. This increases suspicion for an intracerebral hemorrhage (ICH) or ischemic stroke with evolving and dangerous cerebral edema and brainstem compression. Initial steps should focus on preventing further increases in ICP. These include:
- Osmotherapy using mannitol or hypertonic saline
- To decrease cerebral edema and improve blood viscosity
- Hyperventilation if the patient is intubated
- To avoid hypercarbia and induce vasoconstriction
- Analgesia and sedation
- To decrease cerebral metabolic rate which in turn decreases the brain’s cerebral blood flow needs
- Maintain cerebral perfusion pressure
- To decrease further cerebral edema caused by reactive hypertension and hyperemia (see below)
Additional steps that can help include:
- Keeping the head of the bed elevated to at least 30 degrees
- To improve venous outflow though with the caveat that head elevation can decrease arterial perfusion at the height of the brain
- Ensuring the head is midline and ensure C-collar is not too tight
- To maximize outflow from the cerebral veins
- Avoid hyperthermia
- To decrease cerebral metabolic rate
- If intubated, ensure that the tape (or commercial securing device) is not too tight
- To optimize oxygenation and ventilation
The patient is given 50 mcg of fentanyl, however he is increasingly agitated. The left pupil is now 3 mm and sluggish while the right pupil is 2 mm and reactive. The transport team decides to “scoop and run” given there is only a 10-minute transport time. The patient is prepped for transport to the tertiary care centre.
Will you treat a BP of 222/104 en route?
With a 10 min flight to FMC I would not spend any time whatsoever delaying that flight. In flight, labetalol doses to aim for a systolic of 180.
-Gavin Greenfield MD, CCFP-EM.
Not knowing exactly what you are dealing with always makes messing with BP a little concerning, however at this point patient looks like Cushing so I’d give HTS 5cc/kg before worrying about BP.
-Andrew W. Fagan MD, FRCPC
My feeling is that there is more evidence that BP control is not beneficial in stroke but the definitive answer is not clear in the literature. I understand that stroke team wants SBP < 180 to give thrombolytic. But this case is (1) unknown diagnosis – bleed vs infarct and (2) short transport……
So why don’t we just forget about BP control and provide good supportive care, check a glucose, do a gas if we have time, and rapid transport.
-Rob Hall MD FRCPc
You do not have a diagnosis. You are considering ICH or posterior fossa ischemic stroke. The INTERACT2 and ATACH-2 trials specifically addressed the role of aggressive BP control targeting a systolic BP of 140 mmHg compared to a systolic target of 180 mmHg. The INTERACT2 trial in 2013 suggested a benefit based on an ordinal analysis, ATACH2 more clearly demonstrated no benefit of aggressive BP control in ICH. As such, the existing evidence suggests systolic blood pressure targeted below 180 mmHg is just as good as 140 mmHg.
However, if this patient is having an ischemic stroke you would not want to intervene on blood pressure unless over 220 mmHg systolic. This is because collateral blood flow is thought to be blood pressure dependent. If the patient was to get tPA then a systolic BP of 180 mmHg would be appropriate, based largely on inclusion criteria for stroke trials and the risk of ICH following thrombolytic therapy with elevated BP.
The rapid depression in GCS may be more suggestive of hemorrhage but ischemic stroke with cerebral edema and hydrocephalus could account for this as well. There is no evidence to guide the decision in this scenario. Dr Demchuk, a stroke neurologist and director of the Calgary Stroke Program suggests the following:
Prior to CT imaging:
- Do not treat blood pressure unless 210-220 mmHg systolic
Following CT diagnosis is made:
- Target systolic BP of 140-180 mmHg. While the ATACH2 trial did not suggest a difference between a target of 140 mmHg compared to 180 mmHg, more aggressive blood pressure management may decrease hematoma size but the clinical significant of this is uncertain
- Treat ischemic stroke only if over 210-220 mmHg systolic unless they are receiving IV tPA, in which case a target of less than 180/105 mmHg would be appropriate
I am definitely in the lower systolic BP to 140-150 camp once ICH diagnosis made by CT given its safety and marginal efficacy. Getting the BP down within one hour to that target does seem to reduce hematoma expansion slightly. Some feel more evidence needed so only treat to below 180.
Andrew M. Demchuk MD FRCPC
Director, Calgary Stroke Program
Professor, Depts of Clinical Neurosciences and Radiology
The patient is given 20 mg of labetolol slow IV push.
What osmotic agent will you use to treat elevated ICP?
While there is a great debate in the literature with regards to osmotic agents, there are 3 options commonly used in the ED
- Dose: 1 g/kg over 10 mins
- 3% Hypertonic saline (HTS)
- Dose: 250 ml over 10-15 mins
- Sodium Bicarbonate
- Dose: 1-2 Amp slow IV push over 10 mins
While mannitol has traditionally been first line osmotic therapy for elevated ICP, concerns of hypotension secondary to osmotic diuresis have lead some authors to advocate for the use of 3% HTS, which does not cause a diuresis and can be monitored by the sodium level and without need for serum osmols. A meta-analysis by Burgess et al (2016) found no difference between HTS and mannitol in traumatic brain injury. When in doubt, discuss with you neurosurgeon/neurointensivist. If mannitol is to be given, urine output must be monitored and consider inotropes to maintain cerebral perfusion. HTS may not be readily available in your department. If so, then use 3% saline. The osmolarity of 8.4% bicarbonate is 2000 mOsm/liter, which is equivalent to the osmolarity of 5.8% NaCl. Thus, bicarbonate can be thought of as approximating “6% saline”, or twice as powerful as 3% NaCl. Therefore, instead of bolusing with 100 mls of 3% NaCl, you can bolus 50ml of 8.4% bicarbonate (one amp/vial). One to two amps of sodium bicarbonate is available in all EDs and can be given as a slow IV push.
See EMCrit podcast Number 78 for an excellent discussion of this topic.
While en route, the patient develops sonorous respirations, he is no longer obeying commands and is now demonstrating extensor posturing. You decide to perform an expedited intubation.
Will you provide pretreatment for this patient prior to induction for intubation?
Endotracheal intubation in patients with elevated ICP is perilous. This is because we must avoid further ICP elevations. Extensive sensory innervation of the larynx can mean a reflex sympathetic response to laryngoscopy (RSRL) which can increase ICP. While multiple therapies are available and can be used in conjunction, the evidence is mixed as to their effectiveness in isolation.
The evidence is weak that lidocaine adequately blunts the sympathetic response to endotracheal intubation in patients with elevated ICP. Moreover, adverse effects including dysrhythmia and hypotension have been seen in TBI patients undergoing endotracheal intubation. The recommended dose is 1.5 mg/kg IV but to be effective it needs to be given approximately 3 mins prior to intubation.
There is stronger evidence to support the use of opiates such as fentanyl to blunt RSRL associated with intubation. The fentanyl dose is 1-3mcg/kg over 60 seconds 3 minutes prior to intubation.
This agent has the advantages of decreasing cerebral metabolic rate, and increasing seizure threshold. The danger is that diprivan is commonly associated with hypotension, especially in hypovolemic patients, including those that have received mannitol diuresis. A safe dose in an adult male is usually 20-50 mg. The drug is rarely used in pediatrics. Infusions that last several days can be associated with propofol infusion syndrome, especially in high dose, or in patients who are young or of low weight. However, this is a concern for the intensivist, rather than during the brief ED stay.
Importantly, whatever induction agent is used, it is vital to maintain mean arterial pressure, as hypotension will cause further ICP elevation. Therefore induction agent should be used in conjunction with inotropes and vasopressors (such as phenylephrine or norepinephrine), and with great care in any patient at risk of hypotension or who already has elevated ICP. Because induction agents blunt the sympathetic system this can precipitate hypotension, which in turn lowers cerebral perfusion pressure, and further raises the ICP.
What will you use as your induction agent?
Whatever induction agent is used, it is important to stress that hypotension has very detrimental effects on patients with elevated ICP. Etomidate would seem to be an ideal agent, but is not available is all EDs and can be associated with hypotension in patients with adrenal insufficiency. There is less concern than previously regarding the use of ketamine causing clinically significant elevations in ICP, and because it typically increases blood pressure, this may not be an ideal agent. However, there can be a paradoxical hypotension with ketamine in patients who have been sick for a lengthy period.
What paralytic agent will you use?
Rocuronium is increasingly advocated as the more appropriate paralytic agent in RSI in critically ill patients. Succinylcholine can cause transient elevations in ICP due fasciculations associated with infusion, however the clinical significance of this is uncertain.
What are your goals for post intubation care and mechanical ventilation?
It is critical to provide excellent post-intubation analgesia and sedation in order to prevent further ICP elevations. As such, administer infusions of fentanyl and propofol. On again, hypotension which should be assiduously avoided.
Excessive hyperventilation in patients with elevated ICP have been associated with worse outcomes. This is because with a paCO2 below approximately 25mmHg you can cause profound cerebral vasoconstriction which worsens perfusion and therefore exacerbates ischemia and intracranial hypertension. Accordingly, current recommendations suggest a PaCO2 of 35-38 mmHg. In a patient who is actively herniating and is en route to the OR, there is a role for brief hyperventilation but you should be involving a neurosurgeon or neurointensivist at this point.
The patient is intubated following fentanyl pretreatment at a dose of 1.5 mcg/kg. Etomidate and succinylcholine are used for RSI. The patient is started on a fentanyl and propofol infusion. Upon arrival at the tertiary care centre, with a systolic blood pressure of 140-160 mmHg throughout transfer. They are brought immediately to the CT scanner and are found to have a large thalamic and midbrain ICH with obstructive hydrocephalus. An intraventricular drain is placed. Sadly, the patient expired despite ICU care.
Key Learning Points for Management of Elevated ICP
- In patients with ICH, a target systolic blood pressure of 140 mmHg may be preferable, but has not been found to have unequivocal benefits when compared to a target of 180 mmHg.
- In patients with ischemic stroke, blood pressure need not be intervened on unless systolic blood pressure is over 220 mmHg. The subset of patients that receive tPa likely require a target systolic of 180mmHg.
- In the pre-hospital setting, there is no clear evidence regarding optimal blood pressure targets. It is reasonable to not intervene unless systolic blood pressure is over 220 mm Hg.
- Osmotic therapy is a mainstay of elevated ICP prior to neurosurgical intervention. HTS or mannitol are the typical agents used, though bicarbonate can also be used. If mannitol is given, then anticipate diuresis and hypotension.
- When performing expeditious intubation in patients with elevated ICP, consider lidocaine or fentanyl for pretreatment.
- Etomidate and propofol may be the preferred agents to facilitate intubation in hypertensive patients with elevated ICP. It is crucial to avoiding post-intubation hypotension and to maintain adequate sedation and analgesia.
Expert Peer Review by Peter G Brindley MD FRCPC FRCP Edin FRCP Lond
Professor of Critical Care, and NeuroIntensivist, University of Alberta Hospital
Much of what needs to be communicated has been outlined above. To reiterate, we do not know whether this is ischemic (where a SBP of approximately 180mmHg is probably preferable) versus hemorrhagic (where there is some evidence – though not overwhelming evidence- that 140mmHg is likely preferable). Given that we do not yet know which pathology I would merely target 180mmHg while rushing to CT. Much of neurocritical care is about avoiding extremes: whether hypertension, hypotension, hypercarbia or hypoexemia. If indicated I will thrombolyse patient with a SBP of 180mmHg
However, I would stress brain physiology, as this is commonly overlooked. The hypertension associated with a Cushing Triad is a sign of poor brainstem perfusion, it is not merely a number that needs to be “normalized”. Hypertension is the brainstem’s response to decreased cerebral blood flow, and its attempt to restore cerebral blood flow. Unfortunately, hypertension can cause a vicious cycle of increased blood volume and more cerebral edema, which in turn can worsen cerebral blood flow. This is why it is so worrisome. However, the best way to ameliorate hypertension and turn this vicious cycle into a virtuous cycle is to do those things that restore/maintain cerebral blood flow. Do not just focus on dropping the SBP.
Hypertension is best managed by addressing the underlying problem, namely the inadequate cerebral blood flow secondary (in this case) to cerebral edema and which is triggering the reactive hypertension. The underlying problem is addressed using the techniques outlined above (osmotherapy, hyperventilation, sedation, maintaining cerebral perfusion with inotropes etc). As such if you sedate the patient, use osmotherapy and maintain appropriate co2 and o2 levels the BP should come down, and you may not need labetalol or hydralazine. The danger with indiscriminate antihypertensives is that they can cause further brainstem hypoperfusion. This is especially true with patient already on antihypertensives as this can blunt their response to inotropes. In short, treat the patient not the numbers.
As per the explanation above, I would use the lowest dose of induction agents that I believe would blunt airway reflexes but minimize hypotension. I would not use one agent but a combination as all have pluses and minuses, and a combination often allows you to get away with a lower overall amount of induction. In an average size male patient I would use 50-150ug fentanyl and 10-40mg propofol with pretreatment with 100mg of intravenous lidocaine. I would ensure adequate blood pressure using phenylephrine and norepinephrine. This is premixed and is often part of a premedication given in order to avoid any hypotension during of after induction.
With regards to paralytic choice, I use rocuronium in 100% of cases. Its duration is only about 30 minutes which is not going to adversely affect serial examinations or any clinical decisions. Obviously neither agent affect papillary response which is the only thing that truly matters in the first hour. In addition, you typically dare not wake the patient from sedation given the ICP concerns, so you simply rely upon papillary response and the CT image. Rocuronium also avoids any fasiculations (regardless of whether they are truly significant) and all the other relative contraindictations of succinylcholine. The patient will also almost always be maintained on propofol infusion (plus or minus inotropes to maintain pressure, plus or minus a dilantin load) and therefore seizures are not an acute concern either. The idea that you can reverse a patient following succinylcholine also does not hold water in patients with cerebral edema. If you cannot get the tube in they will almost certainly suffer considerable secondary brain injury even during the shorter period of succinylcholine induced apnea. I would almost always use a paralytic to decrease coughing to decrease the required dose of (potentially hypotension causing) induction agents and to maximize likelihood of first pass success.
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