Category Archives: PHARM

Prehospital and Retrieval Medicine

London Trauma Conference Day 2

London Trauma Conference 2013 – Day 2  by Dr Louisa Chan
So I find myself torn today: do I join the the main track with a Major incident theme or the Cardiac Masterclass? I never liked the thought of missing out on anything so I went to a bit of both.
 
Cardiac Masterclass
A lot of people probably think that managing cardiac arrest isn’t challenging and a bit dull because the patient is dead. But the Cardiac Masterclass would inspire you to think of a bright future for cardiac arrest management.
Mark Whitbread reminded us of how important dispatch is in the chain of survival. How much focus do we put on improving bystander CPR rates? Dispatcher assisted CPR has been shown to improve outcomes and needs to be skilfully done.
Ajay Jain pushes for all OHCA patients to be taken to a Cardiac Arrest centre for PCI. Why? Because the results he has from his centre for PCI in OHCA patients results in 77% (101/132) patients surviving to hosp discharge, 65% neurologically intact.
He also tells us that the ECG post arrest is a very poor predictor of PCI findings (although STEMI predicts a positive result) so they all should have PCI.
Lyon-survivors
 
More data from TOPCAT shows us that non survivors of OHCA are easy to cool.
 
LTC-mice
 
 
And maybe we should be cooling DURING cardiac arrest to minimise the reperfusion injury.
 
 
For persistent VF Prof Redwood says revascularisation is the key; when that doesn’t work then reducing LV volume may help so aspiration or an Impella may work. Failing that – ECMO.
 
Major Incidents
Major Incidents by their nature do not happen every day, so experience in these incidents is limited. The challenge then is how can we learn from incidents?
A standardised reporting system for a major incident database would be a good idea – www.majorincidentreporting.org – is where you will find the standard report form and open access database.
And then all I can suggest is that you need to come to the LTC and listen to the accounts of those who have been there. We heard about the Tokyo Sarin attack, Mumbai, and a very compelling story of multiple drownings from Steen Barnung.
Lessons from Tokyo – Sarin attack:

It will happen again
It will be chaos
Crowds cannot be controlled
Comms will fail
Clinical diagnosis – need a senior clinician
Treatment must be immediately available – 3min to absorb sarin
Decontamination – get naked, 90% decon with clothes removal.
Stream casualties
Empower the man on the ground.

 
Gadgets
LTC-MSUThe great thing about the London Trauma Conference is that it’s not just about the content of the tracks, there’s the networking and the opportunity to see new pieces of equipment.
The Norwegians won on the equipment front with their Mobile Stroke Unit. It’s due to go on line in 2014.
So TTFN and more from me on Day 3 of #LTC2013

London Trauma Conference 2013

FDIA_ImageOur inside reporter Dr Louisa Chan provides an update from Day One of the London Trauma Conference:
At risk of sounding like a resuscisaurus, last year was my first foray into the world of blogging. I’m proud to say that the genetic make up of most emergency physicians allows us to adapt so that others do not die! And so here I am again, making my way into the big smoke to report on the great developments of 2013.
I’ve struggled in the past to prise myself away from the main trauma track, it is after all the London Trauma Conference, which has left me curious as to the content of the Cardiac arrest symposium, this year it has been integrated, so I finally get to scratch that itch.
 
Prehospital Cardiac Arrest Management in Scotland
The conference was kicked off by Richard Lyon‘s inspirational description of his TOPCAT study.
In Scotland, of 50 cardiac arrests, 6 will survive to hospital and only 1 will survive to hospital discharge. The survival to hospital discharge in the UK is getting worse (4.8% 1995- 0.7% 2007)
Spurred on by these dreadful figures and a personal quest to improve cardiac arrest care (his father succumbed to a cardiac arrest in his forties)
All in all he has studied 400 cardiac arrest patients pre hospital. So what has he learnt?

  • Precise application of the chain of survival to your own system is vital in the delivery of Quality CPR.
  • He started in the ambulance control room analysing calls (CPR starts at step 11 so more experienced dispatchers skip thee quicker) and worked his way through the chain of survival.
  • The TOPCAT study revealed a 3 min delay to compressions where early intubation and cannulation were performed. Through an education program delivering knowledge and skills with individualised feedback they were able to increase on-chest time.
  • LEADERSHIP was a big factor. Having a clinician dedicated to managing the team improved on chest time and is now delivered by paramedics manning a car response in Edinburgh.
  • Breaks in CPR during movement are overcome by a mechanical chest compression device on carry sheet.
  • Non technical skills are monitored by camera feed
  • These changes have led to a survival to hospital discharge rate of 38% for patients in VF
  • This could translate into an extra 300 lives saved in Scotland when these changes are rolled out nationally.
  • And now there is a move to transport patients who are in VF after the third shock then straight to cath lab.

 
Echocardiography in cardiac arrest
Prof Tim Harris spoke about his passion – echocardiography in resuscitation. If you were in any doubt before then you would leave convinced.
Of course echo should not interfere with CPR so it should be done during the rhythm check with a 10 sec count down.
He covered the usual uses; PEA vs EMD in prognostication (92% sensitivity and 82% specificity to ROSC), Circulation assessment and an estimation of EF (Normal function – anterior mitral valve leaflet hits the septum or is within 5mm , EF 30-45% between 5mm- 18mm and >18mm ant mitral valve leaflets – 30% EF)
 
Cardiogenic shock after cardiac arrest
Professor Deakin: optimising cardiac function after ROSC revolves around the three elements of preload, SVR and myocardial contractility. For those who can still remember how, he recommends preload should be optimised to a LA pressure 15-20mmHg (2-12 normal) with a Swan Ganz catheter.
SVR and contractility can be manipulated thereafter using traditional vasopressors and inotropes or more novel agents like Levosimendan.
Mechanical devices such as IABP, Impella, TandemSupport are useful if available.
Where does the future lie? Perhaps synchronised pacing, hypothermia, extrathoracic ventilation and gene therapy.
LTC-BrohiOpen chest cardiac massage
Prof Karim Brohi: external chest compressions have been around since the 1960′s. Without a doubt external compressions generate a cardiac output, but is this the best way?
Over the last 10 years the priorities in traumatic cardiac arrest have changed – chest compressions are not instituted until after reversible causes have been addressed.
In non traumatic arrest how could we improve?
In canine models coronary perfusion pressure is five times better with internal cardiac massage, providing better survival rates with intact neurology.
There are a few human studies showing marked differences in cardiac index: 1.31 in the open group vs 0.61 in the closed group. In a Japanese study (1993), ROSC was achieved in 58% in open vs 1% closed.
The technique is two handed and the same as that taught in thoracotomy training. The difference is that in medical cardiac arrest you can use a smaller incision ( left lateral).
Who should we use open cardiac massage on? Perhaps in tamponade and pulmonary embolism?
How about when? When 10-15min with “standard care” has failed?
Perhaps it is time for a trial?
Post cardiac arrest syndrome and neuro protective measures
Prof Simon Redwood and Matt Thomas had overlapping talks on this . The bottom line is don’t have too much or too little CO2 or O2. The therapeutic hypothermia debate continues, what is evident is that there should be temperature control to avoid hyperthermia but what temperature? And there may be other benefits to hypothermia eg. limitation of infarct size.
What has been evident from all the speakers today is that it is an integrated system that saves lives and in order to guide the development of your system you need data and the belief that you can improve cardiac arrest outcomes.
More from me tomorrow!
Louisa Chan

Guidelines on prehospital drug-assisted LMA insertion

The UK’s Faculty of Prehospital Care has published a number of consensus guidelines in this month’s EMJ
Dr Minh Le Cong‘s PHARM blog has summaries of three of them:

The final one is the most contentious: Pharmacologically assisted laryngeal mask insertion: a consensus statement(1). Here is the summary:

  1. The PALM technique is an acceptable tool for managing the prehospital airway
  2. The PALM technique is indicated in a rare set of circumstances
  3. The PALM procedure is a rescue technique
  4. The PALM procedure should be checklist driven
  5. At least a second generation SAD should be used
  6. End-tidal CO2 monitoring is mandatory
  7. No preference is expressed for any particular drug
  8. No preference is expressed for any particular dosing regime
  9. Flumazenil is highly unlikely to have a role in managing the PALM patient
  10. The PALM procedure should only be carried out by practitioners of level 7 or above competences
  11. The availability of a trained assistant, familiar with the procedure would be advantageous
  12. The training required to achieve competency in performing the PALM procedure must include in-hospital insertion of SADs, simulation training and training in the transfer of critically ill patients
  13. Data should be collected and collated at a national level for all patients who receive the PALM procedure

They qualify the first point with the statement: The consensus group felt that, in the hands of a specific set of practitioners and in certain circumstances, patients would benefit from the technique. It was recognised that pre-hospital airway management can be very challenging, and deeming the technique unacceptable could deprive patients of a potentially life saving intervention. It was felt that having another tool available to clinicians which could potentially improve patient outcome was important. This was despite the lack of a robust evidence base. It was felt that the technique is indicated in, and should be limited to, a very specific set of circumstances as described below
The publication lists some ‘Organisations represented at the consensus meeting’, which include some commercial training and equipment companies.
It also states that ‘The Royal College of Anaesthetists, although represented at the initial meeting, was unable to support the outcomes agreed by the other represented organisations.
This is a very interesting development. I can see the pros and cons of this. Since practitioners are out there doing PALM anyway, it is in the interests of patients to produce a statement that encourages monitoring, checklists, training, and data collection. To meet all the requirements, one must undergo ‘training in the transfer of critically ill patients’, which would normally necessitate more advanced airway and anaesthesia skills anyway.
A tough one – what would you want if there was no RSI capability but you were hypoxic with trismus and basic airway maneouvres were failing? An all out ban on PALM, or PALM provided by someone trained in surgical airway if it fails (as per the consensus recommendations)?
This and some of the other statements can be downloaded in full at the Faculty of Pre-hospital Care site
1. Pharmacologically assisted laryngeal mask insertion: a consensus statement
Emerg Med J. 2013 Dec;30(12):1073-5

Therapeutic hypothermia does not improve arrest outcome

A paper published today represents to me what’s great about science.
I am impressed with those investigators who had the wherewithall to subject previous therapeutic hypothermia studies to skeptical scrutiny and then design and conduct a robust multicentre trial to answer the question.
One of the criticisms of the original two studies was that those patients who were not actively cooled did not have their temperature tightly controlled, and therefore some were allowed to become hypERthermic, which is bad for brains.
This latest study showed no difference in survival or neurological outcome after cardiac arrest between target temperatures of 33°C and 36°C.
So controlling the temperature after cardiac arrest is still important, but cooling down to the recommended range of 32-4°C is not.
Cool.
Read the full study at the NEJM site.

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

NEJM November 17, 2013 Full text
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BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.

METHODS In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

RESULTS In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.

CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

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Colloids again: still no benefit.

fluidinheloiconIt’s nice to have big randomised trials to guide critical care practice. The age-old crystalloid/colloid debate (is that still going?) has fueled a multicentre and multinational study in 2857 patients with hypovolaemic shock on intensive care units. Patients were classified as having sepsis, trauma, or other causes of hypovolaemic shock.
In the crystalloids group, allowed treatments included isotonic or hypertonic saline and any buffered solutions. In the colloids group, gelatins, albumin from 4-25%, dextrans, and hydroxyethyl starches were permitted.
The primary outcome of 28 day mortality was no different between groups. The study had an open-label design and recruitment took place over nine years.
This finding – no clinical benefit from colloids in critically ill patients – is in keeping with other major ICU trials of colloid therapy: Saline versus Albumin Fluid Evaluation (SAFE), Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP), Scandinavian Starch for Severe Sepsis/Septic Shock (6S), and the Crystalloid versus Hydroxyethyl Starch Trial (CHEST).
Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial
JAMA. 2013 Nov 6;310(17):1809-17
[EXPAND Abstract]

 

IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.

OBJECTIVE: To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.

INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.

MAIN OUTCOMES AND MEASURES: The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.

RESULTS: Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03).

CONCLUSIONS AND RELEVANCE: Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy.

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Prehospital ECLS – it's happening

Patients with refractory (>30 mins) cardiac arrest underwent prehospital cannulation for extracorporeal life support in a French feasibility study. A physician-paramedic team responded by car in Paris to cardiac arrest cases that met inclusion criteria. Mechanical CPR devices (Autopulse or LUCAS) were applied during cannulation. Femoral venoarterial ECMO was instituted using a Maquet Cardiohelp system. Blood products and inotropes, echocardiography, and hypothermia were included in the prehospital management package.
Seven patients were treated, with a mean age of 42 (+/- SD of 16, no median given). ECLS was started an average 57 min (±21) after the onset of ACLS. One patient survived to discharge neurologically intact. Two brain dead patients became organ donors. The survivor had hypertrophic cardiomyopathy with refractory ventricular fibrillation.
Safety and feasibility of prehospital extra corporeal life support implementation by non-surgeons for out-of-hospital refractory cardiac arrest
Resuscitation. 2013 Nov;84(11):1525-9
[EXPAND Abstract]


BACKGROUND: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study.

METHODS AND RESULTS: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22min (±6) after the incision, and 57min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death.

CONCLUSIONS: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival.

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Hyperchloraemia and mortality

Here’s something to add to the pile of data cautioning us to think before we acidify patients with saline. A study in Anesthesia and Analgesia using propensity matching provides retrospective evidence that patients who developed hyperchloremia after noncardiac surgery had worse outcomes.
For more information on why saline isn’t ‘normal’ see: What’s with all the chloride? An assault on salt
Hyperchloremia after noncardiac surgery is independently associated with increased morbidity and mortality: a propensity-matched cohort study
Anesth Analg. 2013 Aug;117(2):412-21
[EXPAND Abstract]


BACKGROUND: The use of normal saline is associated with hyperchloremic metabolic acidosis. In this study, we sought to determine the incidence of acute postoperative hyperchloremia (serum chloride >110 mEq/L) and whether this electrolyte disturbance is associated with an increase in length of hospital stay, morbidity, or 30-day postoperative mortality.

METHODS: Data were retrospectively collected on consecutive adult patients (>18 years of age) who underwent inpatient, noncardiac, nontransplant surgery between January 1, 2003 and December 31, 2008. The impact of postoperative hyperchloremia on patient morbidity and length of hospital stay was examined using propensity-matched and logistic multivariable analysis.

RESULTS: The dataset consisted of 22,851 surgical patients with normal preoperative serum chloride concentration and renal function. Acute postoperative hyperchloremia (serum chloride >110 mmol/L) is quite common, with an incidence of 22%. Patients were propensity-matched based on their likelihood to develop acute postoperative hyperchloremia. Of the 4955 patients with hyperchloremia after surgery, 4266 (85%) patients were matched to patients who had normal serum chloride levels after surgery. These 2 groups were well balanced with respect to all variables collected. The hyperchloremic group was at increased risk of mortality at 30 days postoperatively (3.0% vs 1.9%; odds ratio = 1.58; 95% confidence interval, 1.25-1.98) (relative risk 1.6 or risk increase of 1.1%) and had a longer hospital stay (7.0 days [interquartile range 4.1-12.3] compared with 6.3 [interquartile range 4.0-11.3]) than patients with normal postoperative serum chloride levels. Patients with postoperative hyperchloremia were more likely to have postoperative renal dysfunction. Using all preoperative variables and measured outcome variables in a logistic regression analysis, hyperchloremia remained an independent predictor of 30-day mortality with an odds ratio of 2.05 (95% confidence interval, 1.62-2.59).

CONCLUSION: This retrospective cohort trial demonstrates an association between hyperchloremia and poor postoperative outcome. Additional studies are required to demonstrate a causal relationship between these variables.

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Guidelines for the Management of Heart Failure

Some new guidelines to be aware of are the AHA Guidelines for the Management of Heart Failure. Full text is available free and while comprehensively covering chronic heart failure there is an interesting section on acute decompensated heart failure.
Evidence-based medicine enthusiasts might be interested in recommendations to consider dopamine, nesiritide, and ultrafiltration. These therapies also get a mention in the 2012 European Guidelines. I recommend you review the articles cited in the guidelines to make your own mind up.
Here are a couple of snippets you may find useful:


Snippet from American Guidelines: intravenous loop diuretic doses

“HF patients receiving loop diuretic therapy should receive an initial parenteral dose greater than or equal to their chronic oral daily dose; then dose should be serially adjusted.”


Snippet from European Guidelines: management algorithm for acute heart failure

Click to enlarge

AHF-ESC

2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary
Circulation. 2013 Oct 15;128(16):1810-52 Free Full Text
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012
Eur Heart J. 2012 Jul;33(14):1787-847 Free Full Text

How to Be a Hero

Kal-fly-iconI’m not a hero and don’t claim to be, but when I was given this talk to do for the SMACC 2013 conference I researched the topic and realised I’d worked with several of them.
The talk was the toughest I’ve ever given, because I cried while giving it, and knew that it wouldn’t just be the large audience in front of me who would know I was a wuss, but that it was being recorded for many others to find out too!

A full transcript of the talk, the slide set, and links to references from the talk can be found here.

Lowering the BP rapidly in ICH

ICH-iconIn our retrieval service case reviews, one thing that is that sure to generate discussion is what to do about the blood pressure in patients who present with intracranial haemorrhage and hypertension. We don’t want the bleeding to be worsened by higher blood pressure, but we don’t want to decrease cerebral perfusion pressure in patients who have raised intracranial pressure. Consensus guidelines exist for spontaneous intracerebral haemorrhage and subarachnoid haemorrhage, but they’re not based on strong data.
Here’s a study that attempted to provide more information. Intensive lowering to a target systolic of 140 mmHg within 1 hour was compared with lowering to a target of 180 mmHg. There was no significant reduction in the rate of the primary outcome of death or severe disability. The skeptic in me is disappointed there was no placebo arm. An ordinal analysis of modified Rankin scores favoured the intensive BP-lowering intervention, which means this study can be used by both those for and against intensive BP lowering to support their views.
As explained in an accompanying editorial, a number of factors may limit generalisability to Western practice, such as the predominant use of the alpha-blocking agent urapadil in the large numbers of Asian patients, a drug not available in the United States. Future publication of the ATACH-II trial using intravenous nicardipine will shed more light on this topic.
1. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage
N Engl J Med. 2013 Jun 20;368(25):2355-65
[EXPAND Abstract]


BACKGROUND: Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known.

METHODS: We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician’s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups.

RESULTS: Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively.

CONCLUSIONS: In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure.

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2. Blood pressure in intracerebral hemorrhage–how low should we go?
N Engl J Med. 2013 Jun 20;368(25):2426-7