Brain death in a septic patient: possible relationship with posterior reversible encephalopathy syndrome?
magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures. (MRI) can reveal cerebral infarcts, localised or diffuse leukoencephalopathy and oedematous changes preferentially located in the posterior territories leading to the recognition of a syndrome known as posterior reversible encephalopathy syndrome Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterised by headache, confusion, seizures and visual loss associated with imaging findings of bilateral cortical and subcortical brain edema. (PRES) (3,4). This entity has mainly been described in relationship with some clinical conditions (eclampsia eclampsia (ĭklămp`sēə), term applied to toxic complications that can occur late in pregnancy. Toxemia of pregnancy occurs in 10% to 20% of pregnant women; symptoms include headache, vertigo, visual disturbances, vomiting, , severe arterial hypertension) or treatments (immunosuppressive and antineoplastic antineoplastic /an·ti·neo·plas·tic/ (-ne?o-plas´tik)
1. inhibiting or preventing development of neoplasms; checking maturation and proliferation of malignant cells.
2. an agent that so acts. agents) unrelated to sepsis. It has been suggested that impaired cerebral blood flow autoregulation is one of the causative mechanisms.
We report a fatal case of cerebral posterior ischaemia that was probably triggered by several factors including sepsis.
A 41-year-old man was admitted to our emergency department with dyspnoea dyspnoea
dyspnea. , arterial hypertension and oliguria oliguria /ol·i·gu·ria/ (ol?i-gu´re-ah) diminished urine production and excretion in relation to fluid intake.oligu´ric
Abnormally slight or infrequent urination. leading to acute renal failure acute renal failure Acute kidney failure Nephrology An abrupt decline in renal function, triggered by various processes–eg, sepsis, shock, trauma, kidney stones, drug toxicity-aspirin, lithium, substances of abuse, toxins, iodinated radiocontrast. . He had undergone kidney transplantation more than 20 years previously following the diagnosis of focal glomerulonephritis. Renal function was stable under immunosuppressive therapy with cyclosporine A (CSA) and the patient was usually normotensive normotensive /nor·mo·ten·sive/ (-ten´siv)
1. characterized by normal tone, tension, or pressure, as by normal blood pressure.
2. a person with normal blood pressure. . On admission, he was conscious (Glasgow Coma Scale Glas·gow Coma Scale
A scale for measuring level of consciousness, especially after a head injury, in which scoring is determined by three factors: amount of eye opening, verbal responsiveness, and motor responsiveness. score [GCS] 15/15), but with a high systolic Systolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest. and diastolic pressure (231/123 mmHg). The electrocardiogram was not significantly abnormal. The chest X-ray displayed perihilar congestion The condition of a network when there is not enough bandwidth to support the current traffic load.
congestion - When the offered load of a data communication path exceeds the capacity. and echocardiography Echocardiography Definition
Echocardiography is a diagnostic test that uses ultrasound waves to create an image of the heart muscle. Ultrasound waves that rebound or echo off the heart can show the size, shape, and movement of the heart's valves and revealed mild left ventricular dysfunction. The initial laboratory investigations revealed: serum creatinine 296.14 [micro]mol/l (glomerular filtration rate glomerular filtration rate
n. Abbr. GFR
The volume of water filtered out of the plasma through glomerular capillary walls into Bowman's capsules per unit of time. : 22 ml/min/1.73 [m.sup.2]), CSA plasma concentration 494 ng/ml (usual therapeutic range: 100 to 300 ng/ml). The mean arterial pressure (MAP) was lowered to between 105 and 125 mmHg by nicardipine infusion. Therapy with CSA was discontinued. Twenty-four hours after hospital admission (day two), the patient developed generalised tonic-clonic seizures leading to intensive care unit admission. The brain computed tomogram (CT) performed immediately after this event was unremarkable. However, the patient remained comatose during the following hours with a GCS <8/15. No focal neurological signs were observed and his pupils were not dilated. The arterial blood pressure at this time was 175/98 mmHg (MAP 128 mmHg). The electroencephalogram electroencephalogram /elec·tro·en·ceph·a·lo·gram/ (EEG) (-en-sef´ah-lo-gram?) a recording of the potentials on the skull generated by currents emanating spontaneously from nerve cells in the brain, with fluctuations in potential seen as showed a triphasic wave encephalopathy without epilepti-form changes. The patient became hypoxaemic and orotracheal intubation intubation /in·tu·ba·tion/ (in?too-ba´shun) the insertion of a tube into a body canal or hollow organ, as into the trachea.
endotracheal intubation was performed for mechanical ventilation that was started with an Fi[O.sub.2] at 1.0. The chest X-ray revealed suspected aspiration pneumonia. He progressed rapidly towards septic shock requiring vasopressive support. Methicillin-sensitive Staphylococcus aureus was isolated from the sputum and from the blood cultures. Arterial blood pressure was monitored closely by an invasive radial catheter. The initial objective was to maintain a MAP higher than 65 mmHg. This was achieved by using continuous noradrenaline noradrenaline /nor·adren·a·line/ (nor?ah-dren´ah-lin) norepinephrine.
noradrenaline (nōrˈ· infusion at up to 20 [micro]g/minute. The lowest MAP was 50 mmHg for only 20 minutes. The total duration of noradrenaline infusion was only nine hours and after that, the MAP ranged from 95 to 105 mmHg. On day three, the GCS was 3/15 without any sedative drugs and bilateral mydriasis mydriasis /my·dri·a·sis/ (mi-dri´ah-sis) [Gr.] dilatation of the pupil.
Prolonged abnormal dilation of the pupil of the eye induced by a drug or caused by disease. was noted. The brain CT scan revealed bilateral hypodense lesions in the posterior areas together with cerebral oedema. A few hours later, the patient was declared brain dead according to the clinical, electro-physiological and radiological findings. Post mortem examination could not be obtained.
Sepsis-associated encephalopathy (SAE) is a frequent (50 to 70%) and serious complication of sepsis, recognised as an independent prognostic factor; the mortality increases up to 63% when GCS drops below 8 (2,5-7). The pathophysiology is not completely understood and is multifactorial. It includes inflammatory mediators (such as IFN-alpha, IL-1 or TNF-alpha), activation of the coagulation cascade, metabolic disturbances and drug toxicity. The development of multiple organ dysfunction including hepatic and renal failure also contributes to the encephalopathy (2,6,7). Blood-brain barrier disruption is one of the consequences of the inflammatory response induced by infection, but is not the unique explanation for SAE. Interestingly, human data suggest impairment of cerebral blood flow autoregulation as another relevant pathophysiological mechanism to explain the cerebral dysfunction (8). The clinical presentation of SAE is heterogeneous, ranging from agitation to somnolence. There are no specific diagnostic tests and the diagnosis of SAE is often made after exclusion of other aetiologies. The electroencephalogram can be abnormal, showing different patterns: excessive theta waves, triphasic waves or burst suppression1,2. The brain MRI is usually unremarkable, but in some cases may reveal cerebral infarction or oedematous white matter changes occurring in the posterior cerebral areas (3,4). The treatment relies essentially on the general and aggressive management of sepsis.
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Posterior reversible encephalopathy syndrome is not a specific finding of SAE. PRES was first described in 1996 by Hinchey et al in various clinical conditions, such as immunosuppressive therapy after transplantation, eclampsia, renal nephritis nephritis (nəfrī`təs), inflammation of the kidney. The earliest finding is within the renal capillaries (glomeruli); interstitial edema is typically followed by interstitial infiltration of lymphocytes, plasma cells, eosinophils, and a (autoimmune or toxic) and in the setting of severe hypertension (9). The main clinical findings are headache, vomiting, confusion, seizures and visual impairment. The prognosis is usually good with complete reversibility but, in some cases, when the diagnosis Anaesthesia and Intensive Care, Vol. 37, No. 6, November 2009 is delayed or the treatment not adequate, the outcome can be worse, with permanent damage (10-12). This clinico-radiological syndrome is characterised on brain MRI or CT by white matter oedema most commonly affecting the parietal and occipital lobes but can also spread to other parts of the brain (13). Like SAE, the pathophysiology is not perfectly understood, but probably involves both impaired cerebral blood flow autoregulation and endothelial damage. The role of hypertension is still debated, as is hyperperfusion or hypoperfusion, in oedema formation. The hypertension/hyperperfusion theory is primarily based on blood pressure exceeding the autoregulation limits of the brain. The treatment goals are to decrease the blood pressure when excessive (MAP between 105 and 125 mmHg), to remove the causative agent and to control seizures (10).
However, recent observations support the role of systemic toxicity with hypoperfusion in PRES and the PRES-associated hypertension probably represents a physiological response to the hypoxaemic cerebral oedema (14). A major contribution was made by Bartynski et al, who looked more particularly at the relationships between PRES and infection, sepsis or shock (4). under these conditions, PRES occurred in 25/106 patients. The most common organisms identified in blood cultures were gram-positive cocci cocci /coc·ci/ (kok´si) plural of coccus.
[L.] plural of coccus. . The role of super-antigen-related T-cell stimulation of cytokine release by gram-positive organisms has been discussed in the genesis of PRES. The extent of brain oedema on MRI was greater in the patients who were considered as 'normotensive' (MAP 95 mmHg). These data support the hypothesis of hypoperfusion/vasoconstriction as a possible mechanism of PRES.
The mechanisms leading to cerebral posterior ischaemia in the present case seem multifactorial. The initial diagnosis is probably PRES associated with hypertension and immunosuppressive therapy by CSA in a kidney-transplanted patient who developed acute renal failure responsible for CSA accumulation. Generalised seizures are commonly described both after CSA supratherapeutic concentrations and PRES. The brain CT that was performed immediately after the episode of seizures did not reveal any specific lesion. This does not exclude the diagnosis of early onset PRES. unfortunately, as new complications appeared, it was impossible to confirm this diagnosis by MRI. In a second step, our patient developed gram-positive (methicillin-sensitive Staphylococcus aureus) septic shock caused by aspiration pneumonia. This latest condition, also a potential cause of PRES, was, in our opinion, the precipitating factor leading to cerebral death through a transient and limited decrease in arterial blood pressure. The common feature between SAE and PRES is certainly impaired cerebral autoregulation, particularly in patients with gram-positive sepsis. Although our patient never presented sustained hypotension and required only a short duration of noradrenaline infusion, it can be assumed that this relative hypotension caused irreversible brain injury. While it is now recommended in the Surviving Sepsis Campaign Guidelines to maintain the MAP higher than 65 mmHg in order to avoid tissue hypoperfusion, it appears essential when PRES is suspected in relation to sepsis, to increase mean arterial pressure up to at least 105 mmHg to prevent cerebral ischaemia (15).
In conclusion, we report an extremely unusual complication of a gram-positive septicaemia, despite adequate supportive and haemodynamic management, with a very limited period of relative hypotension. The radiological picture is consistent with previous descriptions of PRES from other various aetiologies. To the best of our knowledge, this is the first description of brain death directly associated with sepsis-related impaired cerebral blood flow autoregulation. As illustrated by the present case, PRES can lead in some instances to irreversible brain damage. This case also emphasises the difficulties in the management of arterial blood pressure when PRES is suspected in a septic patient.
Accepted for publication on April 30, 2009.
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V. HUBERLANT *, G. COSNARD [[dagger]], P. E. HANTSON [[double dagger]]
Department of Intensive Care, Cliniques St-Luc, Universite Catholique de Louvain, Brussels, Belgium
* M.D., Intensivist.
[[dagger]] M.D., Ph.D., Radiologist, Professor, Department of Neuroradiology.
[[double dagger]] M.D., Ph.D., Intensivist, Professor.
Address for correspondence: Dr P. Hantson, Department of Intensive Care, Cliniques St-Luc, Avenue Hippocrate, 10, 1200 Brussels, Belgium. Email: firstname.lastname@example.org