Tag Archives: ventilation

Head Rotation for Mask Ventilation

This is a guest post from Dr Per Bredmose, anaesthetist and retrieval medicine physician in Norway, also known as Viking One

I struggle to ventilate the patient in the resus room, airway pressures are high, the bag doesn’t empty properly. In my mind I plan ahead for the next step. Through my mind goes the thought – is this the one, the one that I cannot ventilate? Statistically it is not likely to be, but I am prepared to add two-person technique, airway adjuncts like nasopharyngeal or oropharyngeal, or supraglottic devices that I use frequently in theatre. I feel confident in the use of these methods, and (in the worst case) in cricothyroidotomy. I have practiced that numerous times on our live-tissue course on anaesthetised pigs. However – before I start any of these actions.. I routinely, almost as a reflex from theatre turn the patient’s head 45 degrees to the left, and then the bag suddenly empties easily – and I can ventilate the patient.

Some people think that time with TIVA in theatre has little value for emergency medicine and advanced prehospital care. I strongly disagree. This is some of the most relevant and valuable time I have for keeping and optimising my practical skills. Bag-valve-mask (BVM) ventilation is an essential core skill for any prehospital provider. In theatre this manoeuvre is well known and frequently practiced. It is my impression that this head rotation is less used, and even maybe less well known outside theatre, and especially in the prehospital field. Therefore this is a reminder of an old technique.

When to do it: When encountering difficulties in conventional BVM ventilation, either when you cannot ventilate or when it’s just difficult to ventilate.

How to do it: Keep a firm one hand grip and gently rotate the head 45 degrees towards the side of the hand with the jaw grip. At the same time, one can try to optimise the one-hand-jaw thrust that goes along with BVM ventilation. Occasionally one needs to extend (dorsiflex) the neck a bit further to fully open the airway. The technique can also be used as a two-person technique, although this is rarely needed.

Opposition: Frequently I hear that I cannot transfer practice from theatre to the prehospital field. Well, this seems to work well in theatre, in ICU and in the field – airways are airways!!

Recently an article in European Journal of Anaesthesiology by Itagaki et al(1) with a cross over design showed an increase in tidal volume when the patients were ventilated in a head rotated position compared to neutral position with the same airway pressure. Their conclusion was as follows: Head rotation of 45° in anaesthetised apnoeic adults significantly increases the efficiency of mask ventilation compared with the neutral head position. Head rotation is an effective alternative to improve mask ventilation if airway obstruction is encountered. Therefore – this is a useful tool that one always should have in the “practical toolbox”. It is not always the solution, but occasionally it saves you (and the patient) a lot of trouble.

Thoughts from Dr Cliff Reid
I haven’t used this approach and wasn’t aware of previous research showing an increase in the retroglossal (but not retropalatine) spaces in (awake) patients with head rotation(2).

The mechanism is thought to be gravitational. It is also possible that neck rotation increases upper airway wall tension that reduces collapsibility of the lumen.

In this elegantly designed new study, a two handed BMV technique was used, similar to that advocated in my prehospital & emergency medicine environments. The rotation was always to the right, although the authors comment that they would expect the same results on the left. The increased tidal volume effect with head rotation occurred mostly in younger patients and patients with Mallampati classification I. Such patients are unlikely to be difficult to mask-ventilate, limiting the applicability of these findings to patients who are difficult to ventilate. However having one more option to employ to improve BMV efficacy (after two person technique, optimising ear-to-sternal-notch positioning, and inserting oro- and/or nasopharyngeal airways) may be useful, and the experience and perspective of my anaesthetic colleague Viking One is definitely food for thought. Obviously one should avoid this if there is potential neck injury so I won’t be trying it my trauma patients.


1. Itagaki T, Oto J, Burns SM, Jiang Y, Kacmarek RM, Mountjoy JR. The effect of head rotation on efficiency of face mask ventilation in anaesthetised apnoeic adults. Eur J Anaesthesiol. 2017 Jul;34(7):432–40.

2. Ono T, Otsuka R, Kuroda T, Honda E, Sasaki T. Effects of head and body position on two- and three-dimensional configurations of the upper airway. J Dent Res. 2000 Nov;79(11):1879–84.

Avoiding intubation in ARDS with awake ECMO

ECMOillusiconA letter in Intensive Care Medicine by Hoeper and colleagues from Hannover describes a small case series of six ARDS patients with severe hypoxaemia who went straight from non-invasive ventilation to awake veno-venous ECMO. All had single organ failure and four were immunocompromised, the latter factor influencing the decision to try to avoid invasive mechanical ventilation. Four of the six patients survived to hospital discharge. A larger multicentre study is being planned.

Clinical illustration courtesy of Dr Brian Burns

Extracorporeal membrane oxygenation instead of invasive mechanical ventilation in patients with acute respiratory distress syndrome
Intensive Care Med. 2013 Nov;39(11):2056-2057 (no abstract)

TracMan results

The TracMan trial – a multicentre randomised trial of early vs late tracheostomy in ICU patients – has been published, showing no difference in the primary outcome of mortality.

A review of the trial is posted on the excellent PulmCCM blog:

There was no proven difference between groups in 30-day mortality (30.8% early vs. 31.5% late, primary outcome), nor in any other outcome including 2-year mortality.

Patients getting early tracheostomies required fewer days of sedation, and there was a suggestion of a reduction of -1.7 ventilator days with early trach (mean 13.6 days vs 15.2 days, p=0.06). However, ICU stays were exactly equal at a median 13 days.

Also, 7% of patients had significant bleeding attributed to their tracheostomies (defined as needing IV fluids or another intervention); this amounted to 11 patients in the early group and 8 in the late group.

PulmCCM is an excellent free resource that will deliver critical care updates to your inbox. It has a number of other useful features, like free board review questions – highly recommended!

Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial
JAMA. 2013 May 22;309(20):2121-9

IMPORTANCE: Tracheostomy is a widely used intervention in adult critical care units. There is little evidence to guide clinicians regarding the optimal timing for this procedure.

OBJECTIVE: To test whether early vs late tracheostomy would be associated with lower mortality in adult patients requiring mechanical ventilation in critical care units.

DESIGN AND SETTING: An open multicentered randomized clinical trial conducted between 2004 and 2011 involving 70 adult general and 2 cardiothoracic critical care units in 13 university and 59 nonuniversity hospitals in the United Kingdom.

PARTICIPANTS: Of 1032 eligible patients, 909 adult patients breathing with the aid of mechanical ventilation for less than 4 days and identified by the treating physician as likely to require at least 7 more days of mechanical ventilation.

INTERVENTIONS: Patients were randomized 1:1 to early tracheostomy (within 4 days) or late tracheostomy (after 10 days if still indicated).

MAIN OUTCOMES AND MEASURES: The primary outcome measure was 30-day mortality and the analysis was by intention to treat.

RESULTS: Of the 455 patients assigned to early tracheostomy, 91.9% (95% CI, 89.0%-94.1%) received a tracheostomy and of 454 assigned to late tracheostomy, 44.9% (95% CI, 40.4%-49.5%) received a tracheostomy. All-cause mortality 30 days after randomization was 30.8% (95% CI, 26.7%-35.2%) in the early and 31.5% (95% CI, 27.3%-35.9%) in the late group (absolute risk reduction for early vs late, 0.7%; 95% CI, -5.4% to 6.7%). Two-year mortality was 51.0% (95% CI, 46.4%-55.6%) in the early and 53.7% (95% CI, 49.1%-58.3%) in the late group (P = .74). Median critical care unit length of stay in survivors was 13.0 days in the early and 13.1 days in the late group (P = .74). Tracheostomy-related complications were reported for 6.3% (95% CI, 4.6%-8.5%) of patients (5.5% in the early group, 7.8% in the late group).

CONCLUSIONS AND RELEVANCE: For patients breathing with the aid of mechanical ventilation treated in adult critical care units in the United Kingdom, tracheostomy within 4 days of critical care admission was not associated with an improvement in 30-day mortality or other important secondary outcomes. The ability of clinicians to predict which patients required extended ventilatory support was limited.

Thenar eminence based medicine

thumbs-upA recent study showed superior effectiveness of one bag-mask ventilation style over another in novice providers. The technique recommended is the thenar eminence grip, in which downward pressure is applied with the thenar eminences while the four fingers of each hand pull the jaw upwards toward the mask.

Interestingly, in their crossover study in which the thenar emininence (TE) technique was compared with the traditionally taught ‘CE’ technique, they demonstrated a ‘sequence effect’. If subjects did TE first, they maintained good tidal volumes when doing CE. However if they did CE first, they achieved poor tidal volumes which were markedly improved when switching to TE.

The authors suggest: “A possible explanation for this sequence effect is that the TE grip is superior. When one used the TE grip first, he or she was more likely to learn how a good tidal volume “feels” and then more likely to apply good technique with the EC grip.“.

Some of us have been practicing and teaching this technique for a while. None have put it better than the brilliant Reuben Strayer of EM Updates in this excellent short video:

Emergency Ventilation in 11 Minutes from reuben strayer on Vimeo.

Efficacy of facemask ventilation techniques in novice providers
J Clin Anesth. 2013 May;25(3):193-7

STUDY OBJECTIVE: To determine which of two facemask grip techniques for two-person facemask ventilation was more effective in novice clinicians, the traditional E-C clamp (EC) grip or a thenar eminence (TE) technique.

DESIGN: Prospective, randomized, crossover comparison study.

SETTING: Operating room of a university hospital.

SUBJECTS: 60 novice clinicians (medical and paramedic students).

MEASUREMENTS: Subjects were assigned to perform, in a random order, each of the two mask-grip techniques on consenting ASA physical status 1, 2, and 3 patients undergoing elective general anesthesia while the ventilator delivered a fixed 500 mL tidal volume (VT). In a crossover manner, subjects performed each facemask ventilation technique (EC and TE) for one minute (12 breaths/min). The primary outcome was the mean expired VT compared between techniques. As a secondary outcome, we examined mean peak inspiratory pressure (PIP).

MAIN RESULTS: The TE grip provided greater expired VT (379 mL vs 269 mL), with a mean difference of 110 mL (P < 0.0001; 95% CI: 65, 157). Using the EC grip first had an average VT improvement of 200 mL after crossover to the TE grip (95% CI: 134, 267). When the TE grip was used first, mean VTs were greater than for EC by 24 mL (95% CI: -25, 74). When considering only the first 12 breaths delivered (prior to crossover), the TE grip resulted in mean VTs of 339 mL vs 221 mL for the EC grip (P = 0.0128; 95% CI: 26, 209). There was no significant difference in PIP values using the two grips: the TE mean (SD) was 14.2 (7.0) cm H2O, and the EC mean (SD) was 13.5 (9.0) cm H2O (P = 0.49).

CONCLUSIONS: The TE facemask ventilation grip results in improved ventilation over the EC grip in the hands of novice providers.

High flow nasal cannula oxygen

Where I work high flow humidified nasal cannula oxygen (HFNC) is used for infants with bronchiolitis and our ICU also employs it for selected adult patients. This is a relatively recent addition to our choice of oxygen delivery systems, and many emergency physicians may still be unfamiliar with it.

A recent review outlines the (scant) evidence for its use in neonates, infants, and adults, and proposes some mechanisms for its effect.

It’s a bit like the traditional delivery of oxygen via nasal cannulae. However, it is recommended that flow rates above 6 l/min are heated and humidified, so the review referred to heated, humidified, high flow nasal cannulae (HFNC).

HFNC began as an alternative to nasal CPAP for premature infants. There are as yet no definitive studies showing its superiority over CPAP.

HFNC may decrease the need for intubation when compared to standard nasal cannula in infants with bronchiolitis.

No hard outcome data yet exist. It has mainly been used for hypoxemic respiratory failure rather than patients with hypercarbia such as COPD patients.

How it works
The following are proposed mechanisms for improvements in gas exchange / oxygenation:

1. A high FiO2 is maintained because flow rates are higher than spontaneous inspiratory demand, compared with standard facemasks and low flow nasal cannulae which entrain a significant amount of room air.

2. Nasopharyngeal dead space ‘washout’. The additional gas flow within the nasopharyngeal space may  reduce dead space: tidal volume ratio. There are some animal neonatal data to show improved CO2 clearance with flows up to 8 l/min.

3. Stenting of the upper airway by positive pressure may decrease upper airways resistance and reduce work of breathing.

4. Some positive pressure (akin to CPAP) may be generated, which can help recruit lung and decrease ventilation–perfusion mismatch; however this is not consistently present in all studies, and high flows are needed to generate even modest pressures. For example, in a study on postoperative cardiac surgery patients, HFNC at 35 l/min generated a nasopharyngeal pressure of only 2.7 ± 1 cmH2O.


Drawbacks and things to know

Studies suggest that if benefit is going to be seen in adult or paediatric patients, this should be evident in the first 30-60 minutes.

Any modest positive pressure generated will be reduced by an open mouth or when there is a significant leak between the cannulae and the nares.

HFNC maintain a fixed flow and generate variable pressures, and the pressures may be more inconsistent in patients with respiratory distress with high respiratory rates and mouth breathing. Compare this with non-invasive ventilation (CPAP and or BiPAP) in which variable flow is used to generate a fixed pressure.


The authors’ summary is helpful:

We postulate that the predominant benefit of HFNC is the ability to match the inspiratory demands of the distressed patient while washing out the nasopharyngeal dead space. Generation of positive airway pressure is dependent on the absence of significant leak around the nares and mouth and seems less likely to be a predominant factor in relieving respiratory distress for most patients.

NIV such as CPAP and bilevel positive airway pressure should still be considered first line therapy in moderately distressed patients in whom supplementation oxygen is insufficient and when a consistent positive pressure is indicated.

There are numerous ongoing trials which should hopefully clarify indications for HFNC and the mechanisms by which it may be beneficial.

An earlier summary of the evidence was written by my Scandinavian chums. And Reuben Strayer uses it to optimise oxygenation during RSI as a modification of the NODESAT technique.

Use of high flow nasal cannula in critically ill infants, children, and adults: a critical review of the literature
Intensive Care Med. 2013 Feb;39(2):247-57

BACKGROUND: High flow nasal cannula (HFNC) systems utilize higher gas flow rates than standard nasal cannulae. The use of HFNC as a respiratory support modality is increasing in the infant, pediatric, and adult populations as an alternative to non-invasive positive pressure ventilation.

OBJECTIVES: This critical review aims to: (1) appraise available evidence with regard to the utility of HFNC in neonatal, pediatric, and adult patients; (2) review the physiology of HFNC; (3) describe available HFNC systems (online supplement); and (4) review ongoing and planned trials studying the utility of HFNC in various clinical settings.

RESULTS: Clinical neonatal studies are limited to premature infants. Only a few pediatric studies have examined the use of HFNC, with most focusing on this modality for viral bronchiolitis. In critically ill adults, most studies have focused on acute respiratory parameters and short-term physiologic outcomes with limited investigations focusing on clinical outcomes such as duration of therapy and need for escalation of ventilatory support. Current evidence demonstrates that HFNC generates positive airway pressure in most circumstances; however, the predominant mechanism of action in relieving respiratory distress is not well established.

CONCLUSION: Current evidence suggests that HFNC is well tolerated and may be feasible in a subset of patients who require ventilatory support with non-invasive ventilation. However, HFNC has not been demonstrated to be equivalent or superior to non-invasive positive pressure ventilation, and further studies are needed to identify clinical indications for HFNC in patients with moderate to severe respiratory distress.

High Frequency Oscillation Trial Results

Here’s a heads up on a major evidence-based medicine event in critical care: the results of two long awaited randomised controlled trials assessing high-frequency oscillation (HFOV) in Acute Respiratory Distress Syndrome (ARDS) have both been published, and the full text is available from the New England Journal of Medicine at the links below.

In summary, the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE)(1) and the Oscillation in ARDS (OSCAR)(2) trials showed no improvement in in-hospital death or 30 day mortality, respectively. OSCILLATE was terminated early on the basis of a strong signal for increased mortality with HFOV.

An editorial discusses some of the reasons why these outcomes were seen, which include among other factors the possibility that they were related to increased requirements for sedation, paralysis, and vasoactive drugs in the HFOV patients that were not offset by improvements in oxygenation and lung recruitment.

1. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome
NEJM 22 Jan 2013

BACKGROUND Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes

METHODS In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause.

RESULTS On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01).

CONCLUSIONS In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254, and ClinicalTrials.gov numbers, NCT00474656 and NCT01506401.)

2. High-Frequency Oscillation for Acute Respiratory Distress Syndrome
NEJM 22 Jan 2013

BACKGROUND Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage.

METHODS In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization

RESULTS There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO2:FiO2 ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression).

CONCLUSIONS The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number, ISRCTN10416500.

Not just in ARDS

A ‘lung protective’ ventilation strategy that includes low tidal volumes has been shown to improve outcomes in patients with ARDS. Many also advocate it as sensible practice for any ventilated patient as a means of minimising the chances of ventilator-induced lung injury and hopefully improving outcome. A recent meta-analysis provides further evidence to support that recommendation:

Context Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS.

Objective To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS.

Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012.

Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations.

Data Extraction Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.

Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, −0.51; 95% CI, −0.70 to −0.32; I2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, −0.06 to 0.27; I2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results.

Conclusions Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation.

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome – A Meta-analysis
JAMA. 2012;308(16):1651-1659

Don’t bronchodilators work in infants?

Inpatient paediatric teams can be scornful when bronchodilators are given by ED staff to wheezing infants, correctly referring to the lack of evidence of clinical benefit(1). There is however a persisting meme out there I’ve heard on a number of occasions that ‘young infants don’t have the receptors so inhaled beta agonists will never work.’ I’d love to know where this comes from.

Apparently, beta 2-receptors are present from the 16th gestational week(2). Pulmonary function testing of ventilated, very-low-birth-weight babies has shown that some consistently responded to beta-agonists whereas others did not(3). A newly published study reports that a quarter of mechanically ventilated infants with bronchiolitis were responders to inhaled albuterol, defined as a reduction in respiratory system resistance more than 30% below baseline(4).

In summary: beta-agonist bronchodilators have not been shown to improve clinical outcomes in wheezing infants. However some infants with some wheezing disorders will show a response in terms of pulmonary function. The receptors are there, and in life-threatening presentations bronchodilators should certainly be considered.

1. Short acting beta agonists for recurrent wheeze in children under 2 years of age
Cochrane Database Syst Rev. 2002;(3):CD002873

BACKGROUND: Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable.
OBJECTIVES: To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze.
SEARCH STRATEGY: Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol

SELECTION CRITERIA: Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease.
DATA COLLECTION AND ANALYSIS: Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used.

MAIN RESULTS: The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home.

REVIEWER’S CONCLUSIONS: There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

2. The beta-2-agonists in asthma in infants and young children
Arch Pediatr. 2002 Aug;9 Suppl 3:384s-389s

Beta 2-agonists, by inducing a fast and long relaxation of the bronchial smooth muscle, are considered as the more potent bronchodilators. beta 2-receptors are present from the 16th gestational week, explaining a possible bronchial response in the youngest children. beta 2-agonists do not induce any bronchodilator response in healthy children. Short-acting beta 2-agonists (salbutamol or albuterol, terbutaline) are indicated for asthma attacks, as needed in chronic asthma, and for prevention of symptoms during effort. They are safe and secure. The more efficient route of administration in preschool children is pressurized metered-dose inhaler used with a spacer device. Therefore, whatever the route of inhalation chosen (inhalation, injection, or continuous nebulization in acute asthma attack), more specified indications and doses are needed in young children. Long-acting beta 2-agonists (formoterol, salmeterol) are not authorized in France in children under 4 to 5 years of age depending on the drug used. Because of new oral formulations and recent considerations about their use in asthma attack, instead of short-acting beta 2-agonists, their indication in preschool asthmatic children might be reconsidered.

3. Use of a beta-agonist in ventilated, very-low-birth-weight babies: a longitudinal evaluation
Dev Pharmacol Ther. 1990;15(2):61-7

To determine if there is a specific postnatal (PNA) or postconceptional age (PCA) at which ventilated preterm infants respond to beta-agonists, we evaluated 15 infants with a mean gestational age of 26.5 +/- 1.5 weeks and mean birth weight of 0.89 +/- 0.23 kg who required mechanical ventilation at 10 days of age. Weekly pulmonary function testing (PFT) was performed before and 1 h after administration of albuterol. Taking the group as a whole, as well as individual babies, regression analysis showed no relationship between positive response and either PNA or PCA. Evaluation of individual infants, however, showed that some consistently responded to beta-agonists whereas others did not. We recommend individual PFT to identify those infants who will benefit from use of beta-agonists.

4. Pulmonary mechanics following albuterol therapy in mechanically ventilated infants with bronchiolitis
J Asthma. 2012 Sep;49(7):688-96

BACKGROUND AND AIMS: Bronchiolitis is a common cause of critical illness in infants. Inhaled β(2)-agonist bronchodilators are frequently used as part of treatment, despite unproven effectiveness. The purpose of this study was to describe the physiologic response to these medications in infants intubated and mechanically ventilated for bronchiolitis.

MATERIALS AND METHODS: We conducted a prospective trial of albuterol treatment in infants intubated and mechanically ventilated for bronchiolitis. Before and for 30 minutes following inhaled albuterol treatment, sequential assessments of pulmonary mechanics were determined using the interrupter technique on repeated consecutive breaths.

RESULTS: Fifty-four infants were enrolled. The median age was 44 days (25-75%; interquartile range (IQR) 29-74 days), mean hospital length of stay (LOS) was 18.3 ± 13.3 days, mean ICU LOS was 11.3 ± 6.4 days, and mean duration of mechanical ventilation was 8.5 ± 3.5 days. Fifty percent (n = 27) of the infants were male, 81% (n = 44) had public insurance, 80% (n = 41) were Caucasian, and 39% (n = 21) were Hispanic. Fourteen of the 54 (26%) had reduction in respiratory system resistance (Rrs) that was more than 30% below baseline, and were defined as responders to albuterol. Response to albuterol was not associated with demographic factors or hospitalization outcomes such as LOS or duration of mechanical ventilation. However, increased Rrs, prematurity, and non-Hispanic ethnicity were associated with increased LOS.

CONCLUSIONS: In this population of mechanically ventilated infants with bronchiolitis, relatively few had a reduction in pulmonary resistance in response to inhaled albuterol therapy. This response was not associated with improvements in outcomes.

Unknown unknowns and pleural effusions

There are plenty of unknowns when it comes to management of pleural effusions on the ICU, which led to a paper with an eye-catching title1.

Mechanically ventilated patients frequently have pleural effusions detected by radiological investigations. Whether to drain them is a common conundrum for intensivists. A systematic review of the literature showed that drainage often improves oxygenation and has a low complication rate2.

While it may have the added advantage of assisting diagnosis and guiding therapy, there is a paucity of literature demonstrating improved patient-orientated outcomes with the routine drainage of pleural effusions in ventilated patients.


1. A pseudo-Rumsfeldian approach to pleural effusions in mechanically ventilated patients.
Crit Care. 2011 Mar 11;15(2):132 Free Full Text

2. Utility and safety of draining pleural effusions in mechanically ventilated patients: a systematic review and meta-analysis.
Crit Care. 2011;15(1):R46 Free Full Text

INTRODUCTION: Pleural effusions are frequently drained in mechanically ventilated patients but the benefits and risks of this procedure are not well established.

METHODS: We performed a literature search of multiple databases (MEDLINE, EMBASE, HEALTHSTAR, CINAHL) up to April 2010 to identify studies reporting clinical or physiological outcomes of mechanically ventilated critically ill patients who underwent drainage of pleural effusions. Studies were adjudicated for inclusion independently and in duplicate. Data on duration of ventilation and other clinical outcomes, oxygenation and lung mechanics, and adverse events were abstracted in duplicate independently.

RESULTS: Nineteen observational studies (N = 1,124) met selection criteria. The mean PaO2:FiO2 ratio improved by 18% (95% confidence interval (CI) 5% to 33%, I2 = 53.7%, five studies including 118 patients) after effusion drainage. Reported complication rates were low for pneumothorax (20 events in 14 studies including 965 patients; pooled mean 3.4%, 95% CI 1.7 to 6.5%, I2 = 52.5%) and hemothorax (4 events in 10 studies including 721 patients; pooled mean 1.6%, 95% CI 0.8 to 3.3%, I2 = 0%). The use of ultrasound guidance (either real-time or for site marking) was not associated with a statistically significant reduction in the risk of pneumothorax (OR = 0.32; 95% CI 0.08 to 1.19). Studies did not report duration of ventilation, length of stay in the intensive care unit or hospital, or mortality.

CONCLUSIONS: Drainage of pleural effusions in mechanically ventilated patients appears to improve oxygenation and is safe. We found no data to either support or refute claims of beneficial effects on clinically important outcomes such as duration of ventilation or length of stay.

Ventilated patients better able to communicate pain with dexmedetomidine

A multicentre European trial on intensive care units showed dexmedetomidine was non-inferior to midazolam or propofol in achieving target sedation levels, but patients were better able to communicate pain compared with midazolam and propofol. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam, but not compared with propofol.

Context Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α2-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

Objective To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients’ interaction with nursing care.

Design, Setting, and Patients Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251).

Interventions Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials.

Main Outcome Measures For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients’ ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223).

Results Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients’ interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001).

Conclusions Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients’ ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine.

Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials
JAMA. 2012 Mar 21;307(11):1151-60