Category Archives: Resus

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Acute Med, All Updates, ICU, Resus

Thrombolysis for PE after limb surgery

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A patient develops shock and dyspnoea on the orthopaedic ward after a total knee replacement and massive pulmonary embolism is confirmed radiologically. Would you give a fibrinolytic or is it contraindicated? Harry Wright and colleagues did, but before giving 50 mg of intravenous rtPA they applied a tourniquet (Cryocuff) to the limb to limit the proportion of the systemic thrombolytic agent that would reach the site of the surgery. The tourniquet was inflated just before the infusion and was left on for one hour. There was some oozing of blood from the postoperative wound, which settled with bandage compression. The authors state that the inflation time of one hour was sufficient for the thrombolytic agent to be largely eliminated from the circulation, since alteplase has a plasma half-life of less than five minutes, although some plasminogen activator activity does persist for up to four hours.

The patient was well at three month follow up. They suggest:

Given the success in this case, we believe that major limb surgery no longer represents a contraindication to thrombolysis.

Thrombolysis for postoperative pulmonary embolism: limiting the risk of haemorrhage
Thorax. 2011 May;66(5):452

All Updates, ICU, Resus

Disposable flexible intubating scope

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There is now a single use flexible intubating device that compares favourably with conventional fibreoptic devices. It does not have fibreoptic cables, but rather has a small camera at its tip illuminated by an LED. The image is transmitted via a cable in the device to a reusable screen. Dr Cook’s team in Bath, England have an extensive track record of evaluating new airway devices, and they report their assessment of this gadget in a manikin-based study. I think this may extend the airway management options to departments or teams for whom the cost and maintenance of conventional fibreoptic equipment is prohibitive.

We compared the Ambu aScope™ with a conventional fibrescope in two simulated settings. First, 22 volunteers performed paired oral and nasal fibreoptic intubations in three different manikins: the Laerdal Airway Trainer, Bill 1 and the Airsim (a total of 264 intubations). Second, 21 volunteers intubated the Airway Trainer manikin via three supraglottic airways: classic and intubating laryngeal mask airways and i-gel (a total of 66 intubations). Performance of the aScope was good with few failures and infrequent problems. In the first study, choice of fibrescope had an impact on the number of user-reported problems (p=0.004), and user-assessed ratings of ease of endoscopy (p<0.001) and overall usefulness (p<0.001), but not on time to intubate (p=0.19), or ease of railroading (p=0.72). The manikin chosen and route of endoscopy had more consistent effects on performance: best performance was via the nasal route in the Airway Trainer manikin. In the second study, the choice of fibrescope did not significantly affect any performance outcome (p=0.3), but there was a significant difference in the speed of intubation between the devices (p=0.02) with the i-gel the fastest intubation conduit (mean (SD) intubation time i-gel 18.5(6.8)s, intubating laryngeal mask airway = 24.1(11.2)s, classic laryngeal mask airway = 31.4(32.5)s, p=0.02). We conclude that the aScope performs well in simulated fibreoptic intubation and (if adapted for untimed use) would be a useful training tool for both simulated fibreoptic intubation and conduit-assisted intubation. The choice of manikin and conduit are also important in the success of such training. This manikin study does not predict performance in humans and a clinical study is required.

Evaluation of a single-use intubating videoscope (Ambu aScopeTM) in three airway training manikins for oral intubation, nasal intubation and intubation via three supraglottic airway devices
Anaesthesia. 2011 Apr;66(4):293-9

All Updates, ICU, Resus

Remifentanil for awake intubation

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Awake fibreopic intubation (AFOI) is indicated in a subgroup of critically ill patients in whom RSI is contraindicated due to a predicted difficult airway, and in whom time pressures do not mandate a more immediate route to the airway. Last night I intubated a patient with a swollen tongue using this technique, under remifentanil sedation. It was interesting to subsequently see that this month’s Anaesthesia contains an article on ‘remi’ for AFOI:

Remifentanil is increasingly being used as the primary agent to provide sedation during awake fibreoptic nasal intubation. In this observational study, we aimed to determine the optimal effect site concentration of remifentanil, using a target controlled infusion based on the Minto pharmacological model, to provide optimal safe intubation conditions without the use of other sedatives/premedication and/or spray-as-you-go local anaesthesia. Twenty patients with anticipated difficult airway participated in the study. Good intubating conditions were achieved in all patients with mean (SD) effect site concentration of 6.3 (3.87) ng.ml(-1) of remifentanil recorded at nasal endoscopy and 8.06 (3.52) ng.ml(-1) during tracheal intubation. No serious adverse event occurred during any of these procedures. These preliminary findings suggest that this is a feasible and safe technique for awake fibreoptic nasal intubation.

Remifentanil as single agent to facilitate awake fibreoptic intubation in the absence of premedication
Anaesthesia. 2011 May;66(5):368-72
Those of us not familiar with target controlled infusions might find a dose in micrograms per kilo more helpful. This paper from Analgesia and Anesthesia provides a useful guide, comparing relatively high and low doses of loading and maintenance doses:

Awake nasotracheal fiberoptic intubation requires an anesthetic management that provides sufficient patient comfort, adequate intubating conditions, and stable hemodynamics. Short-acting and easily titratable analgesics are excellent choices for this maneuver. In this study, our aim was to determine an appropriate dosage regimen of remifentanil for awake nasotracheal fiberoptic intubation. For that reason, we compared two different dosage regimens. Twenty-four patients were randomly assigned to receive remifentanil 0.75 micro g/kg in bolus, followed by a continuous infusion of 0.075 micro g x kg(-1) x min(-1) (Group L), or remifentanil 1.5 micro g/kg in bolus, followed by a continuous infusion of 0.15 micro g x kg(-1) x min(-1) (Group H). All patients were premedicated with midazolam 0.05 mg/kg IV and glycopyrrolate 0.2 mg IV. Both dosage regimens ensured patient comfort and sedation. Discomfort did not differ between groups. Patients in Group H were sedated more profoundly. Hemodynamic stability was maintained with both remifentanil doses. Intubating conditions were adequate in all patients and comparable between the groups. The large dosage regimen did not result in any additional benefit compared with the small dosage. For awake nasotracheal fiberoptic intubation, we therefore recommend remifentanil 0.75 micro g/kg in bolus followed by continuous infusion of 0.075 micro g x kg(-1) x min(-1), supplemented with midazolam 0.05 mg/kg

Awake nasotracheal fiberoptic intubation: patient comfort, intubating conditions, and hemodynamic stability during conscious sedation with remifentanil
Anesth Analg. 2003 Sep;97(3):904-8 (Free Full Text)

 
An alternative to bolus + maintenance is using an incremental infusion rate via an infusion pump. In a comparision with midazolam and fentanyl, remifentanil was given to 37 patients in incremental dosages (0.1-0.25-0.5 microg/kg/min) by an infusion pump according to comfort, level of sedation and respiratory depression. Nasotracheal intubation was better tolerated in the remifentanil group, who also showed better suppression of haemodynamic effects of intubation.

BACKGROUND: Awake fiberoptic intubation is the standard of care for difficult airway management. Quality and success of this technique depend on the experience of the intubating physician and the proper preparation of the patient. The aim of this study was to compare remifentanil (R) as single agent to the combination of fentanyl (F) and midazolam (M), which have been the drugs for analgesia and sedation for this procedure.
METHODS: Seventy-four adult patients requiring nasotracheal intubation were randomly assigned to one of two groups. In group I, (n=37) R was administered in incremental dosages (0.1-0.25-0.5 microg/kg/min) by an infusion pump according to comfort, level of sedation and respiratory depression. In group II, (n=37) analgesia and sedation was achieved by F 1.5 microg/kg and doses of between 1 and 10 mg M, titrated to the individual needs. Patient reactions like grimacing, movement and coughing during intubation were assessed, as well as patient recall of the procedure. Haemodynamic and respiratory parameters were continuously recorded.
RESULTS: Group I patients better tolerated nasal tube passage (P<0.001) and laryngeal tube advancement (P<0.001) than group II. Remifentanil better suppressed hemodynamic response to nasal intubation (P<0.001). No significant difference in respiratory data was recorded. In group I more recall of the procedure was observed (six vs. zero patients, P<0.05).
CONCLUSION: Remifentanil in high doses, as the single agent for patient preparation for awake fiberoptic intubation seems to improve intubating conditions, quality and reliability of the procedure. However, a higher incidence of recall is to be expected.

Evaluation of remifentanil as single drug for awake fiberoptic intubation
Acta Anaesthesiol Scand. 2002 Apr;46(4):350-4
Some authors advocate dexmedetomidine for AFOI. Remifentanil was compared with dexmedetomidine in a randomised, double-blind trial. Remi was loaded and maintained at the ‘low’ dose as described in the second paper above and was associated with a higher intubation success rate on first attempt than dexmedetomidine (76% vs 38%):

Introduction: Dexmedetomidine (DEX), a centrally acting, selective alpha-2 agonist, with analgesic and sedation properties, has been successfully used for sedation in intensive care units. Remifentanil (REM), an ultra-short acting synthetic opioid, is often used to aid awake fiberoptic intubation (AFOI). As a narcotic, REM has a potential for respiratory depression, whereas DEX does not. This study compares the use of REM and DEX as adjuncts to local anesthetic preparation of the airway for AFOI.
Methods: Thirty adult ASA I-III patients with expected difficult airways were randomized to receive REM or DEX for sedation during AFOI. Operators and assessors were blinded to the drug used. Preoperatively, all patients received 2 mg midazolam intravenously and their airways were topicalized with 4% lidocaine. Patients in the REM group received a bolus of 0.75 mcg/kg over 10 minutes followed by an infusion of 0.075 mcg/kg/min. Patients in the DEX group received a bolus of 0.4 mcg/kg over 10 minutes followed by an infusion of 0.7 mcg/kg/hr. A word and picture set was presented to each patient before any drugs were administered, after loading of either sedative, and following extubation. Heart rate, blood pressure, respiratory rate, SpO2, bispectral (BIS) index level, and Ramsay sedation level (RSS) were recorded. Recall of each 3 sets of pictures and words was assessed at 30 minute intervals for a period of 3 hours after the completion of surgery.
Results: Patient demographics were similar between the 2 groups. All patients’ airways were successfully secured by fiberoptic intubation. Seventy-six percent of REM cases were intubated on the first attempt, as compared to 38% of the DEX cases (p=0.02). Intubation attempts were greater in the DEX group even after adjusting for confounders (OR unadjusted = 5.26, 95% C.I. = 1.19, 25.72; OR adjusted = 4.84, 3.43, 6.82). The DEX group had a higher mean oxygen saturation rate than REM (1.58 higher; 95% C.I. = 0.14, 3.03; p=0.03). Although the incidence of O2 saturation < 90% was greater in the REM group, it was not significant. No apneic episodes occurred and no rescue maneuvers, such as administration of reversal drugs or positive pressure ventilation, were required in either group. There was a lower Ramsey Sedation Scale (RSS) score (lower by = 0.45, 95% C.I. = 0.1142, 0.7792; p=0.008) in the DEX group compared to the REM group. A Kaplan Meier survival analysis showed that DEX patients took longer to attain a RSS of 3 despite reaching a lower RSS score. (Logrank test = 4.00 with one degree of freedom, p=0.0455) The DEX group also had 6.99 lower (95% C.I. = 1.19, 12.79; p=0.018) BIS score compared to the REM group. Generalized estimating equations (xtgee) showed no significance in the recall results with the exception of verbal recall in the DEX group after the initial bolus. Minimal hemodynamic instability was observed in both groups.
Discussion: Both Dex and REM can be safely used as sedative agents for AFOI. Despite increased sedation and lower recall after the initial bolus, the DEX group required more attempts at intubation. Nonetheless, lower oxygen saturation was observed in the REM group.

Dexmedetomidine vs. Remifentanil for Sedation in Awake Intubations-A Randomized, Double-Blind Trial
Anesthesiology 2008; 109 A14

Acute Med, All Updates, ICU, Resus

Saving mothers' lives

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The eighth Report of the Confidential Enquiries into Maternal Deaths in the UK investigates the deaths of 261 women who died in the triennium 2006–08, from causes directly or indirectly related to pregnancy.
Direct deaths (from medical conditions that can only be the result of pregnancy) significantly decreased from 6.24 per 100 000 maternities in the last triennium to 4.67 per 100 000 maternities in this triennium (P = 0.02). This equates to 25 fewer direct maternal deaths over the triennium, and this decline is predominantly the result of reductions in deaths from thromboembolism, and to a lesser extent, haemorrhage. The case fatality rate for ectopic pregnancy has almost halved from an estimated rate of 31.2 per 100 000 estimated ectopic pregnancies in 2003–05 to 16.9 in this triennium.
Although Direct maternal deaths have decreased overall there has been a dramatic increase in deaths related to genital tract sepsis, particularly from community-acquired Group A streptococcal disease. The overall rate has increased from 0.85 deaths per 100 000 maternities in 2003–05 to 1.13 deaths in this triennium. Sepsis is now the commonest cause of Direct maternal deaths in the UK and this has prompted a Clinical Briefing from the Centre for Maternal and Child Enquiries (CMACE) alerting health professionals to the risks.
Indirect maternal death rates have remained largely unchanged since the last report. Cardiac disease remains the most common cause of Indirect maternal death: many of these women also had lifestyle-related risk factors for cardiac disease: obesity, smoking and increased maternal age.
The review revealed many of the deaths to be associated with substandard care, some of the challenges being:

  1. Improving clinical knowledge and skills.
  2. Identifying very sick women.
  3. Improving the quality of serious incident/serious untoward incident (SUI) reports.
  4. Improving senior support.
  5. Better management of higher risk women.
  6. Pre-pregnancy counselling.
  7. Better referrals.
  8. Improving communication or communication skills, including: poor or non-existent teamworking; inappropriate or overly short telephone consultations; poor sharing of information between health professionals, particularly the maternity care team and GPs; poor interpersonal skills.

ABSTRACT In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006–2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Saving Mothers’ Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom
BJOG. 2011 Mar;118 Suppl 1:1-203 (Full text available from CMACE site)

All Updates, PHARM, Resus, Trauma

Military vascular injury to the torso is deadly

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Outcomes are described for military personnel with vascular injury sustained in Afghanistan and Iraq.

BACKGROUND: Military injuries to named blood vessels are complex limb- and life-threatening wounds that pose significant difficulties in prehospital and surgical management. The aim of this study was to provide a comprehensive description of the epidemiology, treatment and outcome of vascular injury among service personnel deployed on operations in Afghanistan and Iraq.
METHODS: Data from the British Joint Theatre Trauma Registry were combined with hospital records to review all cases of vascular trauma in deployed service personnel over a 5-year interval ending in January 2008.
RESULTS: Of 1203 injured service personnel, 110 sustained injuries to named vessels; 66 of them died before any surgical intervention. All 25 patients who sustained an injury to a named vessel in the abdomen or thorax died; 24 did not survive to undergo surgery and one casualty in extremis underwent a thoracotomy, but died. Six of 17 patients with cervical vascular injuries survived to surgical intervention; two died after surgery. Of 76 patients with extremity vascular injuries, 37 survived to surgery with one postoperative death. Interventions on 38 limbs included 19 damage control procedures (15 primary amputations, 4 vessel ligations) and 19 definitive limb revascularization procedures (11 interposition vein grafts, 8 direct repairs), four of which failed necessitating three amputations.
CONCLUSION: In operable patients with extremity injury, amputation or ligation is often required for damage control and preservation of life. Favourable limb salvage rates are achievable in casualties able to withstand revascularization. Despite marked progress in contemporary battlefield trauma care, torso vascular injury is usually not amenable to surgical intervention.

Outcome after vascular trauma in a deployed military trauma system
Br J Surg. 2011 Feb;98(2):228-34

Acute Med, All Updates, ICU, Resus

CHEST study to evaluate starch

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No results to report here, just a heads up that the CHEST study is underway: a randomised controlled trial of 7000 patients comparing of 6% hydroxyethyl starch (130/0.4) with 0.9% sodium chloride for all fluid resuscitation needs whilst in the intensive care unit (ICU).  This is how the authors explain the rationale for the study:

Much of the evidence currently available to inform clinicians on the efficacy and safety of starch solutions for fluid resuscitation involves studies conducted using older, high molecular weight and high molar substitution starches. Meta-analyses of these studies suggest that when comparing starches to other fluids, the relative risk of mortality ranges from 1.00 (95% CI 0.80–1.25) to 1.35 (95% CI 0.94–1.95) and for kidney failure 1.50 (95% CI 1.20–1.87). There are insufficient data, however, on the newer low molecular weight, low molar substitution starches. To date, most published studies on these newer generation starches have been conducted in perioperative settings with small sample sizes and limited follow-up. They have been designed to examine surrogate outcomes and not important patient outcomes such as mortality or renal failure.

It is possible to overdo the starch

 
These are some of the same people who brought us the SAFE study on albumin and the NICE-SUGAR study on glycaemic control, so this will be one to watch. It is anticipated that recruitment will be completed by December 2011.

PURPOSE: The intravenous fluid 6% hydroxyethyl starch (130/0.4) (6% HES 130/0.4) is used widely for resuscitation but there is limited information on its efficacy and safety. A large-scale multi-centre randomised controlled trial (CHEST) in critically ill patients is currently underway comparing fluid resuscitation with 6% HES 130/0.4 to 0.9% sodium chloride on 90-day mortality and other clinically relevant outcomes including renal injury. This report describes the study protocol.
METHODS: CHEST will recruit 7,000 patients to concealed, random, parallel assignment of either 6% HES 130/0.4 or 0.9% sodium chloride for all fluid resuscitation needs whilst in the intensive care unit (ICU). The primary outcome will be all-cause mortality at 90 days post-randomisation. Secondary outcomes will include incident renal injury, other organ failures, ICU and hospital mortality, length of ICU stay, quality of life at 6 months, health economic analyses and in patients with traumatic brain injury, functional outcome. Subgroup analyses will be conducted in four predefined subgroups. All analyses will be conducted on an intention-to-treat basis.
RESULTS AND CONCLUSIONS: The study run-in phase has been completed and the main trial commenced in April 2010. CHEST should generate results that will inform and influence prescribing of this commonly used resuscitation fluid.

The Crystalloid versus Hydroxyethyl Starch Trial: protocol for a multi-centre randomised controlled trial of fluid resuscitation with 6% hydroxyethyl starch (130/0.4) compared to 0.9% sodium chloride (saline) in intensive care patients on mortality
Intensive Care Med. 2011 May;37(5):816-823

Acute Med, All Updates, ICU, Resus

Hyperbaric O2 for the sick and the well with CO poisoning

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A French study, large by hyperbaric oxygen trial standards, did not confirm that hyperbaric oxygen therapy improves recovery from pure CO poisoning. In addition, in comatose patients, repeating hyperbaric oxygen therapy resulted in worse outcomes compared to one session.

I don't care if it doesn't work - something looking like a retro-sci-fi time machine is COOL.

INTRODUCTION: Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial.
OBJECTIVES: To assess HBO in patients poisoned with CO.
DESIGN: Two prospective randomized trial on two parallel groups.
SETTING: Critical Care Unit, Raymond Poincaré Hospital, Garches, France.
SUBJECTS: Three hundred eighty-five patients with acute domestic CO poisoning.
INTERVENTION: Patients with transient loss of consciousness (trial A, n = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n = 86) or 4 h of NBO plus one HBO session (arm A1, n = 93). Patients with initial coma (trial B, n = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n = 105). PRIMARY ENDPOINT: Proportion of patients with complete recovery at 1 month.
RESULTS: In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47-1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23-0.79)].
CONCLUSION: In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.

Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials
Intensive Care Med. 2011 Mar;37(3):486-92

All Updates, PHARM, Resus

Pre-hospital Airtraq use often failed

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The Airtraq seems nifty when you try it on a manikin, but until now the question of whether it would be a useful pre-hospital tool was unanswered. This Austrian study provides helpful data:

OBJECTIVES: The optical Airtraq laryngoscope (Prodol Meditec, Vizcaya, Spain) has been shown to have advantages when compared with direct laryngoscopy in difficult airway patients. Furthermore, it has been suggested that it is easy to use and handle even for inexperienced advanced life support providers. As such, we sought to assess whether the Airtraq may be a reliable alternative to conventional intubation when used in the prehospital setting.
DESIGN, SETTING, AND PATIENTS: Prospective, randomized control trial in emergency patients requiring endotracheal intubation provided by anesthesiologists or emergency physicians responding with an emergency medical service helicopter or ground unit associated with the Department of Anesthesiology, General Hospital, Wiener Neustadt, Austria.
MEASUREMENTS AND MAIN RESULTS: During the 18-month study period, 212 patients were enrolled. When the Airtraq was used as first-line airway device (n=106) vs. direct laryngoscopy (n=106), success rate was 47% vs. 99%, respectively (p<.001). Reasons for failed Airtraq intubation were related to the fiber-optic characteristic of this device (i.e., impaired sight due to blood and vomitus, n=11) or to assumed handling problems (i.e., cuff damage, tube misplacement, or inappropriate visualization of the glottis, n=24). In 54 of 56 patients where Airtraq intubation failed, direct laryngoscopy was successful on the first attempt; in the remaining two and in one additional case of failed direct laryngoscopy, the airway was finally secured employing the Fastrach laryngeal mask. There was no correlation between success rates and body mass index, age, indication for airway management, emergency medical service unit, or experience of the physicians. CONCLUSIONS: Based on these results, the use of the Airtraq laryngoscope as a primary airway device cannot be recommended in the prehospital setting without significant clinical experience obtained in the operation room. We conclude that the clinical learning process of the Airtraq laryngoscope is much longer than reported in the anesthesia literature.

Use of the Airtraq laryngoscope for emergency intubation in the prehospital setting: A randomized control trial
Crit Care Med. 2011 Mar;39(3):489-93

Acute Med, All Updates, ICU, Kids, PHARM, Resus, Trauma

Salt or sugar on the brain

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A meta-analysis suggests hypertonic saline may be more effective at lowering intracranial pressure than mannitol. An accompanying editorial cleverly entitled ‘Salt or sugar on the brain: Does it matter except for taste?’ suggests one reason hypertonic saline (HTS) has not replaced mannitol in clinical practice is that too many different regimens of HTS, in terms of concentration, dose, bolus vs. continuous infusions, and plus or minus supplementation of colloids, have been utilised. Because only 112 patients with 184 episodes of increased ICP were treated with each medication in this meta-analysis, the editorialist agrees with the authors in suggesting a larger randomised study is needed.

OBJECTIVES: Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis.
DATA SOURCES: We searched for relevant studies in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Knowledge.
STUDY SELECTION: Randomized trials were included if they directly compared equiosmolar doses of hypertonic sodium solutions to mannitol for the treatment of elevated intracranial pressure in human subjects undergoing quantitative intracranial pressure measurement.
DATA EXTRACTION: Two investigators independently reviewed potentially eligible trials and extracted data using a preformed data collection sheet. Disagreements were resolved by consensus or by a third investigator if needed. We collected data on patient demographics, type of intracranial pathology, baseline intracranial pressure, osms per treatment dose, quantitative change in intracranial pressure, and prespecified adverse events. Our primary outcome was the proportion of successfully treated episodes of elevated intracranial pressure.
DATA SYNTHESIS: Five trials comprising 112 patients with 184 episodes of elevated intracranial pressure met our inclusion criteria. In random-effects models, the relative risk of intracranial pressure control was 1.16 (95% confidence interval, 1.00-1.33), and the difference in mean intracranial pressure reduction was 2.0 mm Hg (95% confidence interval, -1.6 to 5.7), with both favoring hypertonic saline over mannitol. A mild degree of heterogeneity was present among the included trials. There were no significant adverse events reported.
CONCLUSIONS: We found that hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure. Our meta-analysis is limited by the small number and size of eligible trials, but our findings suggest that hypertonic saline may be superior to the current standard of care and argue for a large, multicenter, randomized trial to definitively establish the first-line medical therapy for intracranial hypertension.

Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: A meta-analysis of randomized clinical trials
Crit Care Med. 2011 Mar;39(3):554-9

All Updates, ICU, Resus

Norepinephrine increases preload

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Noradrenaline (norepinephrine) may improve blood pressure in part through its venoconstriction effects, providing more venous return to the heart which increases cardiac output. A study of septic shock patients supports this.
An accompanying editorial by Drs Milzman and Napoli comments: “This study tells us something we probably already knew, that norepinephrine (NE) has the ability to provide venoconstriction, increase central venous pressure, provide a marginal increase in cardiac output, and improve the MAP in patients with septic shock. Importantly, it also demonstrates that Passive Leg Raise (PLR) continues to be a good predictor of preload responsiveness even in the presence of low doses of NE.”

OBJECTIVE: To assess the effects of norepinephrine on cardiac preload, cardiac index, and preload dependency during septic shock.
DESIGN: Prospective interventional study.
SETTING: Medical Intensive Care Unit.
PATIENTS: We included 25 septic shock patients (62 ± 13 yrs old, Simplified Acute Physiology Score II 53 ± 12, lactate 3.5 ± 2.1 mmol/L, all receiving norepinephrine at baseline at 0.24 [25%-75% interquartile range: 0.12-0.48] μg/kg/min) with a positive passive leg raising test (defined by an increase in cardiac index ≥10%) and a diastolic arterial pressure ≤40 mm Hg.
INTERVENTIONS: We performed a passive leg raising test (during 1 min) at baseline. Immediately after, we increased the dose of norepinephrine (to 0.48 [0.36-0.71] μg/kg/min) and, when the hemodynamic status was stabilized, we performed a second passive leg raising test (during 1 min). We finally infused 500 mL saline.
MEASUREMENTS AND MAIN RESULTS: Increasing the dose of norepinephrine significantly increased central venous pressure (+23% ± 12%), left ventricular end-diastolic area (+9% ± 6%), E mitral wave (+19% ± 23%), and global end-diastolic volume (+9% ± 6%). Simultaneously, cardiac index significantly increased by 11% ± 7%, suggesting that norepinephrine had recruited some cardiac preload reserve. The second passive leg raising test increased cardiac index to a lesser extent than the baseline test (13% ± 8% vs. + 19% ± 6%, p < .05), suggesting that norepinephrine had decreased the degree of preload dependency. Volume infusion significantly increased cardiac index by 26% ± 15%. However, cardiac index increased by <15% in four patients (fluid unresponsive patients) while the baseline passive leg raising test was positive in these patients. In three of these four patients, the second passive leg raising test was also negative, i.e., the second passive leg raising test (after norepinephrine increase) predicted fluid responsiveness with a sensitivity of 95 [76-99]% and a specificity of 100 [30-100]%.
CONCLUSIONS: In septic patients with a positive passive leg raising test at baseline suggesting the presence of preload dependency, norepinephrine increased cardiac preload and cardiac index and reduced the degree of preload dependency.

Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients
Crit Care Med 2011;39(4):689-94