Tag Archives: subarachnoid


Magnesium doesn’t improve SAH outcome

A multicentre RCT showed intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial
Lancet 2012 July 7; 380(9836): 44–49 Free full text


Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.

Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).

Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86–1·08).

Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.

Cardiac arrest caused by subarachnoid haemorrhage

We know that subarachnoid haemorrhage (SAH) can cause cardiac arrest. Some questions we may have about this are:

Questions
  • What proportion of out-of-hospital cardiac arrests (OOHCA) who achieve return of spontaneous circulation (ROSC) are caused by SAH?
  • What is the usual presenting arrest rhythm – VT/VF or non-shockable rhythms?
  • What is the outcome of these patients – do any survive?
  • Do they have other characteristic cardiac features, such as ECG or echo abnormalities?
  • Should we do a head CT on all survivors of out-of-hospital cardiac arrest of uncertain aetiology?


A recent Japanese article in Resuscitation1 is the third from that country to be published on the topic in three years, the other two2,3 coming from different centres and all demonstrating some consistent answers, as do papers published in recent years from Europe4 and North America5:

Answers
  • Rates of SAH in OOHCA patients who achieve ROSC and make it to CT range from 4-16% (even higher if other sources of intracranial haemorrhage are included).
  • Studies consistently demonstrate VT/VF to be very rare – PEA and asystole are by far the commonest presenting arrest rhythms.
  • Almost no patients with this presentation due to SAH survive to hospital discharge.
  • In the most recent study, all patients who survived long enough to get a 12 lead showed ST-T abnormalities and/or QT prolongation, although echocardiograms were mostly normal.
  • Rates of SAH in OOHCA patients who achieve ROSC seem to be sufficiently high to seriously consider head CT in these patients if there is no obvious alternate explanation for the arrest.


1. Clinical and cardiac features of patients with subarachnoid haemorrhage presenting with out-of-hospital cardiac arrest
Resuscitation. 2011 Oct;82(10):1294-7




Background Subarachnoid haemorrhage (SAH) is known as one of the aetiologies of out-of-hospital cardiac arrest (OHCA). However, the mechanisms of circulatory collapse in these patients have remained unclear.


Methods and results We examined 244 consecutive OHCA patients transferred to our emergency department. Head computed tomography was performed on all patients and revealed the existence of SAH in 14 patients (5.9%, 10 females). Among these, sudden collapse was witnessed in 7 patients (50%). On their initial cardiac rhythm, all 14 patients showed asystole or pulseless electrical activity, but no ventricular fibrillation (VF). Return of spontaneous circulation (ROSC) was obtained in 10 of the 14 patients (14.9% of all ROSC patients) although all resuscitated patients died later. The ROSC rate in patients with SAH (71%) was significantly higher than that of patients with either other types of intracranial haemorrhage (25%, n = 2/8) or presumed cardiovascular aetiologies (22%, n = 23/101) (p < 0.01). On electrocardiograms, ST-T abnormalities and/or QT prolongation were found in all 10 resuscitated patients. Despite their electrocardiographic abnormalities, only 3 patients showed echocardiographic abnormalities.


Conclusions The frequency of SAH in patients with all causes of OHCA was about 6%, and in resuscitated patients was about 15%. The initial cardiac rhythm revealed no VF even though half had a witnessed arrest. A high ROSC rate was observed in patients with SAH, although none survived to hospital discharge.


2. Assessing outcome of out-of-hospital cardiac arrest due to subarachnoid hemorrhage using brain CT during or immediately after resuscitation
Signa Vitae 2010; 5(2): 21 – 24 Full Text




Objectives. The clinical course and outcome of out-of-hospital cardiopulmonary arrest (OHCPA) due to subarachnoid hemorrhage (SAH) is unclear. The objective of this study is to clarify them.


Study design. Single- center, observational study. Setting. We usually perform a brain computed tomography (CT) in OHCPA patients who present without a clear etiology (42% of all OHCPA), such as trauma, to determine the cause of OHCPA and to guide treatment.


Patients. The study included OHCPA patients without a clear etiology, who were transferred to our center and who underwent a brain CT during resuscitation.


Methods of measurement. Patients’ records were reviewed; initial cardiac rhythm, existence of a witness and bystander cardiopulmonary resuscitation efforts (CPR) were compared with patients’ outcomes.


Results. Sixty-six patients were enrolled. 72.7% achieved return of spontaneous circulation (ROSC), 71.2% were admitted, 30.3% survived more than 7 days, and 9.1. survived-to-discharge. In 41 witnessed OHCPA, 87.8% obtained ROSC, 85.4% were admitted, and 14.6% survived-to-discharge. All survivors were witnessed. In 25 non-witnessed OHCPA, 48% obtained ROSC and were admitted, and no patients were discharged. Initial cardiac rhythm was ventricular fibrillation (VF), pulseless electrical activity (PEA) and asystole in 3.0%, 39.4%, and 47.0%. In 2 VF patients 50.0% survived-to- discharge, and there was no survivor with PEA or asystole.


Conclusion. This study shows a high rate of ROSC and admission in OHCPA patients with a SAH, and also reveals their very poor neurological outcome. We conclude that the detection of a SAH in OHCPA patients is important to determine the accurate frequency of SAH in this patient group and to guide appropriate treatment of all OHCPA patients.

3. Subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest: A prospective computed tomography study
Resuscitation. 2009 Sep;80(9):977-80




Aim Aneurysmal subarachnoid haemorrhage (SAH) is a relatively common cause of out-of-hospital cardiac arrest (OHCA). Early identification of SAH-induced OHCA with the use of brain computed tomography (CT) scan obtained immediately after resuscitation may help emergency physicians make therapeutic decision as quickly as they can.


Methods During the 4-year observation period, brain CT scan was obtained prospectively in 142 witnessed non-traumatic OHCA survivors who remained haemodynamically stable after resuscitation. Demographics and clinical characteristics of SAH-induced OHCA survivors were compared with those with “negative” CT finding.


Results Brain CT scan was feasible with an average door-to-CT time of 40.0min. SAH was found in 16.2% of the 142 OHCA survivors. Compared with 116 survivors who were negative for SAH, SAH-induced OHCA survivors were significantly more likely to be female, to have experienced a sudden headache, and trended to have achieved return of spontaneous circulation (ROSC) prior to arrival in the emergency department less frequently. Ventricular fibrillation (VF) was significantly less likely to be seen in SAH-induced than SAH-negative OHCA (OR, 0.06; 95% CI, 0.01–0.46). Similarly, Cardiac Trop-T assay was significantly less likely to be positive in SAH-induced OHCA (OR, 0.08; 95% CI, 0.01–0.61).


Conclusion Aneurysmal SAH causes OHCA more frequently than had been believed. Immediate brain CT scan may particularly be useful in excluding SAH-induced OHCA from thrombolytic trial enrollment, for whom the use of thrombolytics is contraindicated. The low VF incidence suggests that VF by itself may not be a common cause of SAH-induced OHCA.


4. Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest
Resuscitation. 2001 Oct;51(1):27-32




Objective: Spontaneous subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest is poorly evaluated. We analyse disease-specific and emergency care data in order to improve the recognition of subarachnoid haemorrhage as a cause of cardiac arrest.


Design: We searched a registry of cardiac arrest patients admitted after primarily successful resuscitation to an emergency department retrospectively and analysed the records of subarachnoid haemorrhage patients for predictive features.


Results: Over 8.5 years, spontaneous subarachnoidal haemorrhage was identified as the immediate cause in 27 (4%) of 765 out-of-hospital cardiac arrests. Of these 27 patients, 24 (89%) presented with at least three or more of the following common features: female gender (63%), age under 40 years (44%), lack of co-morbidity (70%), headache prior to cardiac arrest (39%), asystole or pulseless electric activity as the initial cardiac rhythm (93%), and no recovery of brain stem reflexes (89%). In six patients (22%), an intraventricular drain was placed, one of them (4%) survived to hospital discharge with a favourable outcome.


Conclusions: Subarachnoid haemorrhage complicated by cardiac arrest is almost always fatal even when a spontaneous circulation can be restored initially. This is due to the severity of brain damage. Subarachnoid haemorrhage may present in young patients without any previous medical history with cardiac arrest masking the diagnosis initially.


5. Cranial computed tomography in the resuscitated patient with cardiac arrest
Am J Emerg Med. 2009 Jan;27(1):63-7




Introduction The incidence of out-of-hospital and in-hospital cardiorespiratory arrest from all causes in the United States occurs not infrequently. Postresuscitation care should include the identification of the inciting arrest event as well as therapy tailored to support the patient and treat the primary cause of the decompensation. The application of one particular testing modality, cranial computed tomography (CT) of the head, has not yet been determined. We undertook an evaluation of the use of head CT in patients who were resuscitated from cardiac arrest.


Methods Prehospital (emergency medical services), ED, and hospital records were reviewed for patients of all ages with cardiorespiratory arrest over a 4-year period (July 1996-June 2000). Information regarding diagnosis, management, and outcome was recorded. The results of cranial CT, if performed, and any apparent resulting therapeutic changes were recorded. Patients with a known traumatic mechanism for the cardiorespiratory arrest were excluded.


Results A total of 454 patients (mean age 58.3 years with 60% male) with cardiorespiratory arrest were entered in the study with 98 (22%) individuals (mean age 58.5 years with 53% male) undergoing cranial CT. Arrest location was as follows: emergency medical services, 41 (42%); ED, 11 (11%); and hospital, 46 (47%). Seventy-eight (79%) patients demonstrated 111 CT abnormalities: edema, 35 (32%); atrophy, 24 (22%); extra-axial hemorrhage, 14 (13%); old infarct, 12 (11%); new infarct, 11 (10%); intraparenchymal hemorrhage, 6 (5%); skull fracture, 5 (4%); mass, 3 (2%); and foreign body, 1 (1%). Therapeutic and diagnostic alterations in care were made in 38 (39%) patients—35 abnormal and 3 normal CTs. The following alterations occurred: medication administration, 26; withdrawal of life support, 7; additional diagnostic study, 6; neurologic consultation, 6; and intracranial pressure monitoring. 4. No patient survived to discharge.


Conclusion In this subset of resuscitated patients with cardiac arrest, abnormalities on the head CT were not uncommon. Alterations in management did occur in those patients with abnormalities. The indications and impact of head CT in the population of resuscitated patients with cardiac arrest remain unknown, warranting further investigation.


Early CT may rule out subarachnoid haemorrhage

A multicentre Canadian study challenges the practice of routine lumbar puncture after negative CT in patients with suspected subarachnoid haemorrhage. CT scanning within six hours was highly sensitive, although a few cases of initially misinterpreted CTs “illustrate the importance of having a qualified radiologist with a high level of skill interpreting the head scans in a timely manner“.

Nearly 2% of patients were lost to all follow-up; the authors point out that even if a quarter of these patients could have experienced a subarachnoid haemorrhage, the corresponding negative likelihood ratio for a computed tomography performed within six hours rises to only 0.024 (0.007 to 0.07). They assert:

Such a likelihood ratio could be incorporated into the informed discussion surrounding the risks and benefits of lumbar puncture after negative results on computed tomography for this diagnosis

They point out that when CT imaging is obtained more than six hours after headache onset, clinicians should continue to be cautious because of the decreasing sensitivity for subarachnoid haemorrhage beyond this time.



Objective To measure the sensitivity of modern third generation computed tomography in emergency patients being evaluated for possible subarachnoid haemorrhage, especially when carried out within six hours of headache onset.


Design Prospective cohort study. Setting 11 tertiary care emergency departments across Canada, 2000-9.


Participants Neurologically intact adults with a new acute headache peaking in intensity within one hour of onset in whom a computed tomography was ordered by the treating physician to rule out subarachnoid haemorrhage.


Main outcome measures Subarachnoid haemorrhage was defined by any of subarachnoid blood on computed tomography, xanthochromia in cerebrospinal fluid, or any red blood cells in final tube of cerebrospinal fluid collected with positive results on cerebral angiography.


Results Of the 3132 patients enrolled (mean age 45.1, 2571 (82.1%) with worst headache ever), 240 had subarachnoid haemorrhage (7.7%). The sensitivity of computed tomography overall for subarachnoid
haemorrhage was 92.9% (95% confidence interval 89.0% to 95.5%), the specificity was 100% (99.9% to 100%), the negative predictive value was 99.4% (99.1% to 99.6%), and the positive predictive value was 100% (98.3% to 100%). For the 953 patients scanned within six hours of headache onset, all 121 patients with subarachnoid haemorrhage were identified by computed tomography, yielding a sensitivity of 100% (97.0% to 100.0%), specificity of 100% (99.5% to 100%), negative predictive value of 100% (99.5% to 100%), and positive predictive value of 100% (96.9% to 100%).


Conclusion Modern third generation computed tomography is extremely sensitive in identifying subarachnoid haemorrhage when it is carried out within six hours of headache onset and interpreted by a qualified radiologist


Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study
BMJ. 2011 Jul 18;343:d4277

Magnesium for subarachnoid haemorrhage

Symptomatic cerebral vasospasm occurs in nearly one-third of patients with aneurysmal subarachnoid hemorrhage and is a major cause of disability and mortality in this population.

Magnesium (Mg) acts as a cerebral vasodilator by blocking the voltage-dependent calcium channels.. Experimental studies suggest that Mg also inhibits glutamate release by blocking N-methyl-D-aspartate receptors, decreases intracellular calcium influx, and increases red blood cell deformability; all these changes may reduce the occurrence of cerebral vasospasm and minimise brain ischemic injury occurring after SAH.

One hundred and ten patients within 96 hours of admission for aneurysmal subarachnoid haemorrhage (SAH) were randomised to receive iv magnesium or placebo. Nimodipine was not routinely given. Twelve patients (22%) in the magnesium group and 27 patients (51%) in the control group had delayed ischemic infarction – the primary endpoint (p< .0020; odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12– 0.64). Mortality was lower and neurological outcome better in the magnesium group but these results were not statistically significant.

Larger trials of magnesium in SAH are ongoing.

Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: A randomized, placebo-controlled, clinical study
Crit Care Med. 2010 May;38(5):1284-90

Update September 2012:

A multicentre RCT showed intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial
Lancet 2012 July 7; 380(9836): 44–49 Free full text


Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.

Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).

Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86–1·08).

Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.