Cushing Reflex


Article Author:
Sean Dinallo


Article Editor:
Muhammad Waseem


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
10/17/2019 8:08:50 AM

Definition/Introduction

The Cushing reflex (vasopressor response, Cushing reaction, Cushing effect, and Cushing phenomenon) is a physiological nervous system response to acute elevations of intracranial pressure (ICP) resulting in Cushing’s triad of widened pulse pressure (increasing systolic, decreasing diastolic), bradycardia, and irregular respirations. The Cushing reflex was proposed in 1901 by Dr. Harvey Cushing. He believed that the dramatic increase in blood pressure was a reflex to brainstem ischemia seen in patients with increasing ICP from causes such as intracranial hemorrhage, a mass effect from a tumor, and cerebral edema, to name a few. In cases of increased ICP, cerebral perfusion pressure (CPP) drops as the systolic blood pressure cannot overcome the resistance present in the brain. CPP is the pressure that pushes blood through the cerebrovascular network and is defined by the difference between mean arterial pressure (MAP) and intracranial pressure (ICP).[1] With an acute intracranial pathology that causes a mass effect and increased resistance in intracranial vessels, the only way for the body to perfuse intracranial tissue is through elevating the MAP to restore baseline CPP. Dr. Cushing proposed that systemic vasoconstriction and subsequent rise in systemic blood pressure was a mechanism to overcome increased resistance in the brain, increase the CPP, and prevent further ischemia in the brain.[2]

Issues of Concern

Intracranial pressure and cerebral blood flow are determined by the amount of blood and cerebrospinal fluid (CSF) in the skull, as well as the force exerted by the brain on the inside of the skull. As necessary, autoregulatory mechanisms enable the CSF movement between the brain and spinal subarachnoid space, as well as constriction and dilation of arterioles, to maintain ICP within a normal range (5 mmHg to 15 mmHg). Although daily activities such as breathing, coughing, and lifting can cause transient pressure, autoregulatory mechanisms can respond to such changes (so long as mean arterial pressure (MAP) remains between 50 mmHg to 150 mmHg), and maintain ICP within a normal range.

An increase in intracranial pressure most commonly occurs due to the presence of a space-occupying lesion (e.g., intracranial hemorrhage, hematoma, tumor, or abscess). However, it may also result from cerebral edema (e.g., due to head injury, hypoxic or ischemic encephalopathy, postoperative edema, or ischemic stroke with vasogenic edema), metabolic disorders (e.g., hyponatremia, uremic or hepatic encephalopathy), increased CSF production (e.g., choroid plexus tumor), decreased CSF drainage (e.g., due to flow obstruction by space-occupying lesion, aqueductal stenosis, or Chiari malformation), increased venous pressure (e.g., due to cerebral venous sinus thrombosis, jugular vein obstruction or thrombosis, or heart failure), idiopathic intracranial hypertension, or pseudotumor cerebri.

The Cushing reflex is a physiological nervous system response to acute elevations of intracranial pressure (ICP) resulting in the Cushing triad of widened pulse pressure (increasing systolic, decreasing diastolic), bradycardia, and irregular respirations. In the first stage of the Cushing reflex, blood pressure and heart rate rise in response to sympathetic activation to overcome increases in ICP.[3] This sympathetic response allows for brain perfusion as long as the ICP is not too high to overcome. For the brain to remain adequately perfused, mean arterial pressure (MAP) must be maintained higher than ICP. In the second stage of the Cushing reflex, hypertension continues to be present, but the patient becomes bradycardic rather than tachycardic. There are differing opinions on the mechanisms leading to this stage of the Cushing reflex. The prior thinking was that increased blood pressures lead to activation of baroreceptors in the aortic arch, triggering parasympathetic activation and resultant bradycardia. Tsai et al. proposed that chemoreceptors outside the brain do not participate in this stage, and bradycardia actually results from compression of the intracranial vagal nerve.[4][5][6] It is still not wholly agreed upon as to what causes bradycardia, but there is now a wide acceptance that this is a late-stage and likely terminal sign of worsening intracranial pathology. Blood pressure will continue to rise until the MAP overcomes the ICP, and blood can adequately perfuse the brain, thereby resolving hypoxia and avoiding infarction. In the later stages of the Cushing reflex, brainstem dysfunction secondary to increased ICP, tachycardia, or bradycardia is observable clinically as an irregularity in breathing; this is characterized initially by shallow breaths with occasional periods of apnea. This activity occurs due to compression of the brainstem by increased ICP, and in result, distortion of the respiratory centers.[4] Eventually, agonal breathing may develop as herniation of the brain begins, with progression to respiratory and cardiac arrest. Overall, it seems that the Cushing reflex is the very last hemodynamic response to a systemic sympathetic activation that follows the acute rise in ICP.[7]

Clinical Significance

The Cushing triad, as a result of the Cushing reflex, is typically observed in the later stages of acute head injury. Although the reflex is a homeostatic response by the body in an attempt to rescue under-perfused brain tissues, the Cushing triad is, unfortunately, a late sign of increasing ICP, and indicative that brainstem herniation is imminent. Patients who present to the emergency department with concerns for increased ICP and two of three signs of the Cushing reflex have been found to have almost two-fold higher mortality than patients with normal and stable vital signs. It is, therefore, important to recognize early signs of elevated ICP (e.g., a headache, nausea, vomiting, altered level of consciousness) to intervene as early as possible.[8] Many clinicians use the presence of bradycardia and hypertension as an indication of increased ICP, however, this signals a late-stage Cushing reflex that carries a poor prognosis for the patient. Moving into the future, it may be wise to look for the presence of tachycardia and hypertension in patients with suspected intracranial pathology so that interventions can start promptly.[9]

Cushing reflex is most usually an irreversible condition with a terminal prognosis for the patient. Initial emergency treatments are aimed at rapidly lowering the ICP and include: Elevation of the patient’s head 30 to 45 degrees, mannitol and/or furosemide, which act as an osmotic diuretic, induced hyperventilation, steroids, or cerebrospinal fluid drainage.[10]


  • Image 11689 Not availableImage 11689 Not available
    Image courtesy S Bhimji MD
Attributed To: Image courtesy S Bhimji MD

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Cushing Reflex - Questions

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A 67-year-old male is brought into the emergency department after the sudden onset of right-sided paralysis 45 minutes ago at home. His initial vital signs include a blood pressure of 160/110 mmHg, a heart rate of 75 beats per minute, a respiratory rate of 12 breaths per minute, and a temperature of 98.7 degrees Fahrenheit. He has a past medical history significant for coronary artery disease, atrial fibrillation, and hypertension. His medications include Warfarin, Propanolol, Aspirin, and Atorvastatin. While being wheeled to the CT Scanner, the patient suddenly loses consciousness, and a rapid response is called. His repeat vital signs include a heart rate of 43 beats per minute, a blood pressure of 170/60 mmHg, and a respiratory rate of 7 breaths per minute. What is the most likely etiology for this patient's sudden decompensation?



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Which of the following clinical signs is the most worrisome in a patient whom elevation of intracranial pressure is a concern?



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A 60-year-old male is brought into the emergency department after falling down a flight of stairs in his home. He is making incomprehensible sounds and cannot provide any details as to what occurred, and there is no family with him. Upon initial evaluation, he has a heart rate of 55 beats per minute, a blood pressure of 167/68 mmHg, a respiratory rate of 10 breaths per minute with irregular respirations, a temperature of 98.7 degrees Fahrenheit and oxygen saturation of 88% on room air. His pupils are 6 mm bilaterally and sluggish to light, and there is a 4-cm hematoma on the back of his head. He withdraws to pain upon sternal rub and does not open his eyes to pain or the provider's voice. Which of the following signs is most indicative of poor prognosis in this patient?



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An 82-year-old female was found lying on the floor after an unknown period by her daughter. The daughter states that the patient had weakness on the left side of her body and an inability to speak. Emergency medical services obtained vital signs, which included a blood pressure 175/115 mmHg, a heart rate of 90 beats per minute, a respiratory rate of 12 breaths per minute, and an oxygen saturation of 95% on room air. Upon arrival to the emergency department, her repeat vitals include a blood pressure of 170/80 mmHg, a heart rate of 55 beats per minute, a respiratory rate of 10 breaths per minute, and an oxygen saturation of 92% with a Glasgow coma scale of 9. She has numerous areas of ecchymosis on her body and appears malnourished. There is also a large hematoma on her right forehead. Her right pupil is 7 mm and non-reactive to light, and her right pupil is 4 mm and reactive to light. Which of the following is the best initial step in management?



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A 17-year-old male is brought into the emergency department by paramedics after jumping off a two-story building. When found, he was unresponsive on a cement parking lot. On arrival to the emergency department, the Glasgow Coma Scale is 6 and the patient is immediately intubated for airway protection. On initial evaluation, there is a large area of ecchymosis behind his right ear. Which of the following sets of vital signs indicates impending brain herniation?



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Cushing Reflex - References

References

Smith M, Cerebral perfusion pressure. British journal of anaesthesia. 2015 Oct;     [PubMed]
Wan WH,Ang BT,Wang E, The Cushing Response: a case for a review of its role as a physiological reflex. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2008 Mar;     [PubMed]
Grady PA,Blaumanis OR, Physiologic parameters of the Cushing reflex. Surgical neurology. 1988 Jun;     [PubMed]
Tsai YH,Lin JY,Huang YY,Wong JM, Cushing response-based warning system for intensive care of brain-injured patients. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2018 Dec;     [PubMed]
Pirahanchi Y,Bordoni B, Anatomy, Head and Neck, Carotid Baroreceptors 2019 Jan;     [PubMed]
Lau EO,Lo CY,Yao Y,Mak AF,Jiang L,Huang Y,Yao X, Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors. Frontiers in physiology. 2016;     [PubMed]
Schmidt EA,Despas F,Pavy-Le Traon A,Czosnyka Z,Pickard JD,Rahmouni K,Pathak A,Senard JM, Intracranial Pressure Is a Determinant of Sympathetic Activity. Frontiers in physiology. 2018;     [PubMed]
Bhandarkar P,Munivenkatappa A,Roy N,Kumar V,Samudrala VD,Kamble J,Agrawal A, On-admission blood pressure and pulse rate in trauma patients and their correlation with mortality: Cushing's phenomenon revisited. International journal of critical illness and injury science. 2017 Jan-Mar;     [PubMed]
Kalmar AF,Van Aken J,Caemaert J,Mortier EP,Struys MM, Value of Cushing reflex as warning sign for brain ischaemia during neuroendoscopy. British journal of anaesthesia. 2005 Jun;     [PubMed]
Aronovich D,Scumpia A,Edwards D, Cushing's reflex in a rare case of adult medulloblastoma. World journal of emergency medicine. 2014;     [PubMed]

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