Cabrini 2018

Cabrini et al. Critical Care (2018) 22:6 DOI 10.1186/s13054-017-1927-3 RESEARCH Open Access Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials Luca Cabrini1,2, Giovanni Landoni1,2, Martina Baiardo Radaelli1, Omar Saleh1, Carmine D. Votta1, Evgeny Fominskiy1,3, Alessandro Putzu4, Cézar Daniel Snak de Souza5, Massimo Antonelli6, Rinaldo Bellomo7,8, Paolo Pelosi9* and Alberto Zangrillo1,2 Abstract Background: We performed a systematic review of randomized controlled studies evaluating any drug, technique or device aimed at improving the success rate or safety of tracheal intubation in the critically ill. Methods: We searched PubMed, BioMed Central, Embase and the Cochrane Central Register of Clinical Trials and references of retrieved articles. Finally, pertinent reviews were also scanned to detect further studies until May 2017. The following inclusion criteria were considered: tracheal intubation in adult critically ill patients; randomized controlled trial; study performed in Intensive Care Unit, Emergency Department or ordinary ward; and work published in the last 20 years. Exclusion criteria were pre-hospital or operating theatre settings and simulation-based studies. Two investigators selected studies for the final analysis. Extracted data included first author, publication year, characteristics of patients and clinical settings, intervention details, comparators and relevant outcomes. The risk of bias was assessed with the Cochrane Collaboration’s Risk of Bias tool. Results: We identified 22 trials on use of a pre-procedure check-list (1 study), pre-oxygenation or apneic oxygenation (6 studies), sedatives (3 studies), neuromuscular blocking agents (1 study), patient positioning (1 study), video laryngoscopy (9 studies), and post-intubation lung recruitment (1 study). Pre-oxygenation with non-invasive ventilation (NIV) and/or high-flow nasal cannula (HFNC) showed a possible beneficial role. Post-intubation recruitment improved oxygenation, while ramped position increased the number of intubation attempts and thiopental had negative hemodynamic effects. No effect was found for use of a checklist, apneic oxygenation (on oxygenation and hemodynamics), videolaryngoscopy (on number and length of intubation attempts), sedatives and neuromuscular blockers (on hemodynamics). Finally, videolaryngoscopy was associated with severe adverse effects in multiple trials. Conclusions: The limited available evidence supports a beneficial role of pre-oxygenation with NIV and HFNC before intubation of critically ill patients. Recruitment maneuvers may increase post-intubation oxygenation. Ramped position increased the number of intubation attempts; thiopental had negative hemodynamic effects and videolaryngoscopy might favor adverse events. Keywords: Tracheal intubation, Critically ill, Emergency department, Intensive care unit, Videolaryngoscopy, High flow nasal cannula * Correspondence: ppelosi@hotmail.com 9 Department of Surgical Sciences and Integrated Diagnostics, San Martino Policlinico Hospital, IRCCS for Oncology, University of Genoa, Largo Rosanna Benzi 8, 16131 Genoa, Italy Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Cabrini et al. Critical Care (2018) 22:6 Page 2 of 9 Background with disagreement resolved by consensus under supervi- Critically ill patients frequently require tracheal intubation sion of two investigators (GL and AZ) and, if potentially in the intensive care unit (ICU), in the emergency depart- pertinent, full articles were retrieved. ment (ED), or during in-hospital emergency in general The following inclusion criteria were employed for wards [1–3]. Critically ill patients differ from elective sur- potentially relevant studies: (a) tracheal intubation in gical patients intubated in the operating theatre: often they critically ill patients; (b) RCT; (c) study performed in present with severe respiratory failure, hemodynamic in- adult patients in the ICU, ED or general ward; and (d) stability, increased sensitivity to the side effects of seda- study published in the last 20 years in a peer-reviewed tives, recent food intake, and cardiac or cerebrovascular journal. diseases [2]. Airway management outside the operating Exclusion criteria included pre-hospital or operating theatre has a high rate of major complications, such as se- theatre settings and studies based on simulation. Two vere hypoxia, hemodynamic collapse, cardiac arrest, and investigators (LC and GL) selected studies for the final death [1, 3–6]. Moreover, the incidence of difficult intub- analysis, independently assessing compliance with the ation is high when compared to elective intubation in the selection criteria. Divergences were resolved by operating room [1, 7, 8]. Lack of training, supervision and consensus. assistance, failure to identify patients at risk, failure to plan and carry out a backup strategy if required, and deficiency Data abstraction and study characteristics in available equipment, all are the most relevant modifi- Standardized forms were used to extract data with dis- able risk factors [6]. Other factors that could increase the agreements resolved by discussion or involving a third incidence of adverse events include the emergent reviewer when required. Data, which were extracted fol- requirement of tracheal intubation preventing adequate lowing the patient, population or problem, intervention, preparation, and the commonly limited physical space comparison, outcomes (PICO) approach, included first around ICU beds. Accordingly, interventions to improve author, publication year, characteristics of patients and everyday practice, in particular pre-oxygenation and first- clinical settings (the population), intervention details, attempt success rate, have been proposed and evaluated comparators, relevant outcomes (e.g. indicators of effi- individually or as combined in bundles [2, 3, 9]. However, cacy or safety), and risk of bias. To assess the risk of these protocols are based mostly on expert opinions, low- bias, we used the Cochrane Collaboration’s Risk of Bias quality retrospective or before-after studies, or are derived tool. from guidelines developed for elective intubation in the operating theatre. So far, there has not been a systematic review focused on randomized controlled trials (RCTs). Statistical analysis We performed a systematic review of RCTs evaluating We pooled estimates of treatment effects for each out- any drug, technique, or device aimed at improving the come by random-effects model meta-analysis using the success rate or the safety of tracheal intubation in critic- inverse variance for binary data and Mantel-Haenszel ally ill patients performed in ICU, ED or general ward methods for continuous data. We used the random- settings. When feasible, we also performed a meta- effects model because we anticipated that studies would analytic assessment of these findings. include patients from varied populations, and investiga- tors with different experience for intubation, thereby Methods resulting in the estimation of heterogeneous intervention Search strategy effects. We report continuous outcomes as mean differ- PubMed, BioMed Central, Embase and the Cochrane ence and dichotomous outcomes as risk ratios (RRs) Central Register of Clinical Trials were searched for per- with their 95% confidence interval (CI). When continu- tinent studies (updated 13 November 2017) by five in- ous variables were analyzed as median and interquartile vestigators (LC, MB, OS, CV, and CDSS). The full range or CI we transformed the data using the following PubMed/Medline search strategy is reported in formula: mean = median; with interquartile range stand- Additional file 1: Figure S1. The references of retrieved ard deviation = (3rd quartile - 1st quartile)/1.35; with CI articles were checked for further studies. Moreover, the standard deviation = √sample size x (upper limit – lower investigators scanned pertinent reviews to detect further limit)/3.92, to avoid losing data. We assessed heterogen- studies. No language restriction was enforced. eity using the I2 statistic. We also assessed the p value for the I2 statistic to determine the strength of evidence Study selection for heterogeneity. In accordance with Cochrane guid- References obtained from databases and the literature ance, we did not analyze publication bias because our were first independently examined at title/abstract level search identified fewer than ten studies for each data by six investigators (LC, MB, OS, CV, AP, and CDSS), comparison. We compared treatment effects across Cabrini et al. Critical Care (2018) 22:6 Page 3 of 9 subgroups using a test for interaction. We performed Three studies compared sedatives. Sivilotti et al. com- the analyses using an intention-to-treat approach. We pared thiopental, fentanyl and midazolam (together with conducted two-tailed statistical tests and set the NMBA) during rapid sequence induction in the ED in probability of type I error at 0.05. All calculations 86 critically ill patients [17]: thiopental slightly shortened and graphs were performed using Review Manager the time to intubation but was associated with lower re- (RevMan, Version 5.3, Copenhagen: The Nordic duction in systolic blood pressure compared to fentanyl Cochrane Centre, The Cochrane Collaboration, 2014). and midazolam, while midazolam was associated with an The protocol had been registered in the Prospero increase in heart rate compared to fentanyl and thiopen- database (CRD42017068989). tal. In the second study, alfentanil, sufentanil, and fen- tanyl were compared during rapid sequence intubation (RSI) in the ED in 90 trauma patients [18]: no significant Results difference in hemodynamic parameters was observed. Database searches and scanning of references yielded Finally, Jabre et al. evaluated etomidate versus ketamine 880 articles. From these we finally identified 22 random- in 469 critically ill patients in 12 EDs and 65 ICUs in ized clinical trials for inclusion in seven areas of interest France [19]: no difference in intubation conditions or (Additional file 1: Figure S1): use of a pre-procedure intubation-related adverse events was found. check-list (1 study) [10], pre-oxygenation and apneic In the only RCT on NMBA, succinylcholine was com- oxygenation (6 studies) [11–16], sedatives (3 studies) pared to rocuronium for RSI in 401 ICU patients [20]: [17–19], neuromuscular blocking agents (NMBA) (1 no difference was observed in intubation conditions, rate study) [20], patient’s position (1 study) [21], videolaryn- of success of first attempt, and oxygen desaturation goscopy (9 studies) [22–30], and post-intubation recruit- episodes, but the duration of the intubation sequence ment maneuver (RM) (1 study) [31]. was on average 14 seconds shorter with succinylcholine. One multicenter RCT evaluated the efficacy of a ver- One multicenter trial compared the sniffing position bally performed 10-item pre-intubation checklist [10] (entire bed flat, with the patient’s head elevated) and compared to no checklist in 262 enrolled critically ill pa- ramped position (upper half of the bed raised at an angle tients: no difference was found in any outcome (lowest of 25° and the neck extended to have the patient’s face peripheral oxygen saturation (SpO2), lowest systolic parallel to the ceiling) during laryngoscopy in 260 pa- blood pressure, number and length of intubation tients [21]. The sniffing position allowed a better view of attempts, life-threatening episodes, or in-hospital the glottis across the full range of body mass indices and mortality). prior level of experience, and reduced the number of in- The six RCTs focusing on pre-oxygenation and ap- tubation attempts; however, it did not improve oxygen- neic oxygenation were heterogeneous in treatment ation, hemodynamic, or other clinical outcomes. and comparator groups [11–16]. Pre-oxygenation re- Nine studies compared different models of videolaryn- fers to the administration of oxygen before induction goscopy to direct, traditional laryngoscopy in different (though some oxygen delivery devices used for pre- conditions and settings in 2069 patients (Table 2) oxygenation can then be left on after induction or [22–30]. Time to intubation and first-attempt success even during laryngoscopy). Apneic oxygenation refers rate were the most relevant reported outcomes. to oxygen applied to a patient who is not spontan- Videolaryngoscopy did not shorten the time to intub- eously breathing (i.e. during induction-to-laryngoscopy ation (Fig. 1a), nor the first-pass success rate (Fig. 1b), and laryngoscopy-to-intubation periods). The charac- even when evaluating the studies according to the teristics and findings of these six RCTs (563 patients greater or lesser experience of the operators, or accord- overall) are summarized in Table 1. The two studies ing to the setting (ICU versus ED), or the model used applying non-invasive ventilation (NIV) for pre- (hyper-angulated vs non-hyper-angulated) (Additional oxygenation compared to standard pre-oxygenation file 1: Figures S4 − S6). Four studies [22, 25, 27, 29] ana- showed positive results [11, 13] In a meta-analysis of lyzed the subgroups with anticipated difficult airways: no the five studies applying high-flow nasal cannula study found a difference in the outcomes. The two lar- (HFNC) [12–16], stratified for the application as pre- gest trials found an increased incidence of severe com- oxygenation tool and/or as apneic oxygenation tool, plications in post-hoc analyses when videolaryngoscopy limited evidence suggests that HFNC is ineffective if was employed: Yeatts et al. reported longer duration of used for apneic oxygenation, while it might have the intubation procedure, greater incidence of severe de- some efficacy in improving the levels of lower oxygen saturation episodes and highest mortality rate in the saturation, but without improving the incidence of se- group with severe head injury, while Lascarrou et al. re- vere desaturation if used for pre-oxygenation ported an increased incidence of life-threatening compli- (Additional file 1: Figures S2 and S3). cations [22, 29]. Cabrini et al. Critical Care (2018) 22:6 Page 4 of 9 Table 1 Characteristics of the five studies on pre-oxygenation techniques 1st Journal, Setting Patients’ Pre-oxygenation Pre-oxygenation Primary Comments Author year characteristics intervention comparator outcome Baillard C Am J ICU Severely Pre-oxygenation with Pre-oxygenation Mean drop in SpO2 values were significantly et al. [11] Resp Crit hypoxemic NIV nonrebreather bag-valve SpO2 during better in the NIV group after Care patients mask driven by 15 L/min ETI pre-oxygenation, during Med, oxygen. Patients were intubation, and 5 min after 2006 allowed to breath intubation Episodes of SpO2 spontaneously with < 80% were significantly less occasional assistance common in the NIV group (p < 0.01). Vourc’h M Intensive ICU Severely Pre-oxygenation and HFO by facemask followed by Lowest SpO2 No significant difference in any et al. [12] Care hypoxemic apneic oxygenation no supplemental O2 during throughout peri-procedural oxygenation Med, patients with HFNC laryngoscopy intubation parameter. Duration of 2015 (maintained during procedure mechanical ventilation was laryngoscopy) shorter in the HFNC group. Jaber S Intensive ICU Severely Pre-oxygenation with Pre-oxygenation with NIV Lowest SpO2 Lowest SpO2 during intubation et al. [13] Care hypoxemic NIV plus HFNC, then plus sham HFNC, then apneic during ETI higher in the intervention Med, patients apneic oxygenation oxygenation with sham group. In per-protocol analysis, 2016 with HFNC HFNC (maintained during fewer severe desaturation (maintained during laryngoscopy) episodes in the intervention laryngoscopy) group. Simon M Resp ICU Severely Pre-oxygenation with Bag -valve mask and no Mean lowest No difference at any time et al. [14] Care, hypoxemic HFNC, then apneic supplemental O2 during SpO2 during points in SpO2 or pCO2, and in 2016 patients oxygenation with laryngoscopy ETI procedural-related HFNC (maintained complications. during laryngoscopy) Semler Am J ICU Critically ill Not standardized Not standardized Lowest SpO2 No significant difference in any MW et al. Resp Crit patients pre-oxygenation pre-oxygenation and no between peri-procedural oxygenation [15] Care followed by apneic supplemental O2 during induction and parameter. No difference in Med, oxygenation with laryngoscopy 2 min after short-term and hospital 2016 HFNC during ETI mortality. laryngoscopy Caputo N Acad ED Critically ill Standard 3-min Standard 3-min Average No difference in lowest average et al. [16] Emerg patients pre-oxygenation pre-oxygenation and no lowest SpO2 SpO2, no difference in SpO2 at Med, followed by apneic supplemental O2 during during apnea any time-point, no difference in 2017 oxygenation with laryngoscopy and in the the rates of moderate or severe HFNC during following desaturation episodes. laryngoscopy 2 minutes Abbreviations: ICU intensive care unit, ETI endotracheal intubation, NIV non invasive ventilation, HFNC high-flow nasal cannula, HFO high-flow oxygen, SpO2 peripheral oxygen saturation, PaO2 arterial oxygen pressure, ED emergency department Finally, Constantin JM et al. evaluated the efficacy of arterial PaO2. HFNC for apneic oxygenation seems inef- an RM (40 cmH2O for 30 seconds) immediately after fective; the sniffing position reduced the number of in- successful RSI in 40 ICU hypoxemic patients [31]. The tubation attempts, without improving clinically relevant RM group had significantly higher arterial pO2 both 5 outcomes. No other significant beneficial or negative ef- and 30 minutes after the RM; no difference in fect was observed among the other evaluated interven- hemodynamic parameters was observed, although one tions such as use of a checklist, choice of opioids, choice RM was interrupted due to hypotension. of etomidate versus ketamine, choice of rocuronium ver- sus succinylcholine, and use of a videolaryngoscope Discussion (which on the contrary was associated with increased Key findings adverse events in four trials). We performed a systematic review focusing on RCTs evaluating drugs, techniques or devices aimed at improv- ing the success rate or the safety of tracheal intubation Relationship to previous studies in adult critically ill patients in the ICU, ED or general Tracheal intubation of critically ill patients is a common wards. We identified 22 trials focusing on seven different procedure and is frequently complicated by severe ad- areas. Our main findings were a possible beneficial role verse events, with an incidence ranging from 4.2 to 39% of pre-oxygenation with NIV and/or HFNC, the negative [1, 4–7]. To improve safety or efficacy of the procedure, effect of thiopental on blood pressure, and the possible standardization of the approach was proposed in the efficacy of post-intubation recruitment in increasing form of bundle or checklist [2, 9] including identification Cabrini et al. Critical Care (2018) 22:6 Page 5 of 9 Table 2 Characteristics of the nine studies comparing videolaryngoscopy to direct laryngoscopy 1st Journal, year Setting Patients’ Personnel Videolaryngoscope Primary Comments author characteristics performing ETI model outcome Yeatts DJ J of Trauma Trauma Adult Emergency medicine GlideScope Survival to No difference in the subgroup et al. [22] and Acute resuscitation critically ill residents, hospital with anticipated difficult Care Surg, unit trauma anesthesiology discharge airways. Higher incidence of 2013 patients residents, attending severe desaturation and worse anesthesiologists, mortality in the subgroup of nurse anesthetist head-injured patients intubated with videolaryngoscope Griesdale Can J Anesth, ICU, Adult Medical students or GlideScope Number of No difference in intubation DEG et al. 2012 ordinary critically ill non-anesthesiology intubation attempts. Significantly better [23] ward, ED patients residents attempts visualization in the videolaryngoscope group, but lowest SaO2 during first attempt Kim JW Resuscitation, ED Adult Experienced GlideScope Success rate of No difference in the incidence et al. [24] 2016 patients in intubators ETI by the of esophageal intubation and cardiac arrest intubator tooth injury. Chest compression interruption during CPR were longer in the direct laryngoscopy group Goksu E Turk J Emerg ED Blunt trauma Residents and C-MAC Overall Better glottis visualization and et al. [25] Med, 2016 patients attending physicians successful decreased esophageal of the ED intubation intubation rate with videolaringoscopy. No difference in success rate even separating easy and difficult intubations Janz DR Crit Care ICU Adult Pulmonary and McGrath Mac or Intubation on Better glottis visualization with et al. [26] Med, 2016 critically ill critical care fellows GlideScope or first attempt, videolaryngoscopy. No other patients Olympus adjusted for differences the operator’s previous experience Driver BE Acad ED Adult Senior residents C-MAC First-pass No difference in duration of et al. [27] EmergMed, critically ill success rate first attempt, aspiration, hospital 2016 patients length of stay. No difference in success rate in the subgroup with anticipated difficult airways Sulser S Eur J ED Adult Experienced C-MAC First attempt Better glottis visualization in et al. [28] Anaesth, critically ill anesthesia success rate the videolaryngoscopy group. 2016 patients consultants No difference in desaturation episodes or complications Lascarrou JAMA, 2017 ICU Adult ICU physicians McGrath Mac Successful Better glottis visualization, but JB et al critically ill first-pass higher number of life-threatening [29] intubation complications with videolariyngoscopy. No difference in success rate even stratified for operator experience and expected difficult airways. No difference in number of intubation Silverberg Crit Care ICU and Adult Pulmonary and GlideScope First-attempt Better glottis visualization and MJ et al. Med, 2015 ordinary critically ill critical care fellows success rate lower number of attempts in [30] wards patients the videolaryngoscopy group. No difference in overall complications rate. Neuromuscular blocking agents were not used Abbreviations: ICU intensive care unit, ETI endotracheal intubation, SpO2 peripheral oxygen saturation, CPR cardiopulmonary resuscitation of patients at high risk; pre-oxygenation; monitoring, significant decrease in severe and non-severe complica- specific equipment, drugs, and algorithms. Recently, a tions was observed [3]. However, most of the available 10-point bundle was evaluated in three ICUs: a recommendations on the topic are based on expert Cabrini et al. Critical Care (2018) 22:6 Page 6 of 9 Fig. 1 Videolaryngoscopy vs. direct laryngoscopy: forest plot for intubation time (a) and for first-attempt successful intubation (b) opinion or non-randomized studies. Furthermore, they complementary to pre-oxygenation techniques [34]. are derived from guidelines developed for a different set- Pre-oxygenation before intubation of critically ill pa- ting (elective intubation in the operating theatre) where tients and, above all, of hypoxemic patients, is crucial. airway-management-related deaths are 30-fold less com- However, the techniques commonly applied in the oper- mon than in the ICU and ED and brain damage 60-fold ating room (spontaneous breathing of high concentra- less common [32]. Hence, we decided to perform a tion of oxygen applied by face mask for some minutes, systematic review to identify the best available evidence- followed by manual ventilation by a bag-valve mask) base on the topic, help improve daily practice and in- might be not effective or feasible in the deranged physi- form future research. ology of ICU and ED patients. Our findings suggest that The only RCT comparing a pre-intubation checklist to HFNC might improve pre-oxygenation; on the other no checklist did not find any positive effect [10]: these hand, apneic oxygenation with HFNC seems ineffective. results are in contrast with the above mentioned before- These findings are in line with a recent meta-analysis after study [3], and in line with another observational [35] also including a non-randomized trial: apneic oxy- study [9]. A different choice of items could at least in genation with HFNC reduced severe desaturation in part explain the difference: the positive results were elective intubation in the operating room (OR), but not obtained in a center with extensive experience in intub- in ICU patients with respiratory failure. On the contrary, ation specifically in critically ill patients, while the NIV applied for 3 minutes before laryngoscopy resulted checklist of the RCT derived from the opinions of in a better safety profile reducing the incidence of severe experts in airway management and from guideline- desaturation episodes, without NIV-related complica- recommended steps for intubation, not focused on crit- tions [11]: NIV may be regarded as a useful approach to ically ill patients [9]. The present systematic review pre-oxygenation in critically ill patients, above all in hyp- could contribute to identify the most relevant items to oxemic patients, even if it was evaluated only in a single, be included in future checklists. small study. Pre-oxygenation of patients to be intubated has a Three unrelated heterogeneous RCTs evaluated seda- strong rationale, extending the duration of safe apnea tives. The only large one evaluated etomidate versus during laryngoscopy before the patient reaches critical ketamine, finding no difference [19]: a Cochrane meta- levels of hypoxemia [33]. Apneic oxygenation can be analysis also investigating non-intubation-related adverse Cabrini et al. Critical Care (2018) 22:6 Page 7 of 9 effects of etomidate in critically ill patients concluded ill patients; moreover, videolaryngoscopy might be as- that its use is not associated with worsening of mortality, sociated with an increased incidence of severe adverse organ dysfunction or resource utilization, even if it nega- events. tively affects adrenal gland function [36]. Unfortunately, In a small RCT, an RM after intubation improved oxy- and surprisingly, no RCT evaluated the very commonly genation at 5 and 30 minutes, without any other differ- used sedative propofol in this context. ence in hemodynamic parameters. RM has been Marsch at al. found that succinylcholine and rocuro- evaluated mainly in acute lung injury and acute respira- nium for rapid sequence intubation (RSI) are equivalent, tory distress syndrome, but its role is still debated [50]. even if the duration of intubation was longer with rocur- Based on this single RCT, RM could be useful after in- onium [20]. It should be noted that the study did not tubation in hypoxemic patients, even if its effect declines consider the potential beneficial role of the antagonist after 30 minutes. sugammadex when using rocuronium [37]. Moreover, even if RSI is commonly considered the technique of choice in critically ill patients [38], graded sedation in- Implications of study findings tubation not using NMBA has also been proposed and Our findings imply that, in hypoxemic patients, time applied [28, 37–40]. Unfortunately, the two approaches permitting, pre-oxygenation by NIV and/or HFNC could have never been compared. offer the best safety profile; post-intubation RM can fur- In a multicenter study, the sniffing position during ther enhance arterial oxygenation. The sniffing position laryngoscopy improved the rate of first-attempt success might be the position of choice for laryngoscopy. Thio- rate compared to the ramped position, without improv- pental should be avoided, above all in hemodynamically ing oxygenation and hemodynamic parameters [21]. unstable patients. These findings are in contrast with previous studies, in which the ramped position provided a better view of the glottis [41–43] and seemed to improve pre-oxygenation Strengths and limitations [44, 45]. However, all previous studies were performed The present study has several strengths. It is the first in the operating room in elective patients. systematic review comprehensively evaluating all steps Tracheal intubation of critically ill patients is associ- of tracheal intubation in critically ill patients in every ated with increased frequency of difficult intubation setting (the ICU, ED, and general wards). Moreover, it compared with elective intubation in the operating the- is based only on evidence from RCTs. Our findings atre [1, 7, 8]. Furthermore, multiple attempts at intub- are relevant to the development of evidence-based al- ation are associated with a higher risk of severe gorithms on the topic. Furthermore, we identified the complications, due to the limited physiological reserve lack of data in many areas, hopefully informing future of these patients [5]. Our findings suggest that videolar- research. yngoscopes do not perform better than traditional direct The main limitation of the present systematic re- laryngoscopy across a wide range of conditions, even if view is its inability to offer robust suggestions about they could offer better visualization of the glottis. On crucial areas. In particular, no RCT evaluated the role the contrary, four trials found an increased incidence of and compared the performance of different scores to severe complications when videolaryngoscopy was used predict difficult intubation [2, 9], the best monitoring [22, 29]. Our results are in line with two recent meta- and equipment, the role of supervision, the best asso- analyses of randomized trials on videolaryngoscopy lim- ciated drugs (in particular the role of propofol, a ited to the ICU setting [46, 47], and in contrast with a commonly used sedative), the best way to face pre- previous meta-analysis on videolaryngoscopy in the ICU dicted and unpredicted difficult airways scenarios, the setting also including non-randomized trials and report- role of fiber optic bronchoscopy and supraglottic de- ing an increased first-pass success rate (but not a vices, the best strategy to confirm tracheal intubation, reduction in complications) [48]. Moreover, a recent and how to prevent or treat hemodynamic instability meta-analysis including 64 studies (61 performed in [2, 9]. RCTs and meta-analyses cannot be the only el- elective surgical patients) concluded that videolaryn- ements guiding daily practice, as many aspects remain goscopy may reduce the number of failed intubations, (and will likely remain) unexplored by RCTs. In these particularly among patients with a difficult airway, areas, we still depend largely on expert opinions, low- but no evidence indicates that they reduce the num- quality studies and algorithms developed for the OR. ber of intubation attempts, the incidence of hypoxia As the Fourth National Audit Project conducted in or respiratory complications, and/or the time required the UK on major complications of airway manage- for intubation [49]. Available evidence does not sup- ment concluded, airway management in the ICU and port the routine use of videolaryngoscopy in critically ED is still under-explored [6]. Nevertheless, our Cabrini et al. Critical Care (2018) 22:6 Page 8 of 9 findings allow the definition of more robust evidence- Medicine and Anaesthesiology, Fondazione Policlinico Universitario A. based strategies and will inform future research. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. 7Department of Intensive Care, Austin Hospital, Heidelberg, Australia. 8School of Medicine, The University of Melbourne, Melbourne, Australia. 9Department of Surgical Conclusions Sciences and Integrated Diagnostics, San Martino Policlinico Hospital, IRCCS We identified and meta-analyzed 22 RCTs in seven dif- for Oncology, University of Genoa, Largo Rosanna Benzi 8, 16131 Genoa, Italy. ferent areas, evaluating drugs, techniques or devices aimed at improving the success rate or the safety of tra- Received: 18 September 2017 Accepted: 20 December 2017 cheal intubation in critically ill patients. 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Data sharing is not applicable to this article as no original, unpublished data Scand J Trauma Resusc Emerg Med. 2014;22:41. were generated or analyzed during the current study. 10. Janz DR, Semler MW, Joffe AM, Casey JD, Lentz RJ, deBoisblanc BP, et al. Check-UP Investigators; Pragmatic Critical Care Research Group. A Authors’ contributions multicenter randomized trial of a checklist for endotracheal intubation of LC, GL, EF, and AZ participated in the design of the study and developed the critically ill adults. Chest. 2017;S0012–3692(17):32685–5 search strategy. LC, MBR, OS, CV, AP, and CDSS searched for pertinent 11. Baillard C, Fosse JP, Sebbane M, Chanques G, Vincent F, Courouble P, et al. studies. GL, EF, AP, OS, AM, RB, and PP performed the statistical analysis. LC, Noninvasive ventilation improves preoxygenation before intubation of GL, EF, and AZ helped to draft the manuscript. All authors read and hypoxic patients. Am J Respir Crit Care Med. 2006;174:171–7. approved the final manuscript. 12. Vourc’h M, Asfar P, Volteau C, Bachoumas K, Clavieras N, Egreteau PY, et al. High-flow nasal cannula oxygen during endotracheal intubation in Ethics approval and consent to participate hypoxemic patients: a randomized controlled clinical trial. Intensive Care Not applicable. Med. 2015;41:1538–48. 13. Jaber S, Monnin M, Girard M, Conseil M, Cisse M, Carr J, et al. Apnoeic Consent for publication oxygenation via high-flow nasal cannula oxygen combined with non- Not applicable. invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre, blinded, randomised controlled Competing interests OPTINIV trial. Intensive Care Med. 2016;42:1877–87. The authors declare that they have no competing interest. 14. Simon M, Wachs C, Braune S, de Heer G, Frings D, Kluge S. High-flow nasal cannula versus bag-valve-mask for preoxygenation before intubation in subjects with hypoxemic respiratory failure. Respir Care. 2016;61:1160–7. Publisher’s Note 15. Semler MW, Janz DR, Lentz RJ, Matthews DT, Norman BC, Assad TR, et al. Springer Nature remains neutral with regard to jurisdictional claims in Randomized trial of apneic oxygenation during endotracheal intubation of published maps and institutional affiliations. the critically ill. Am J Respir Crit Care Med. 2016;193:273–80. 16. Caputo N, Azan B, Domingues R, Donner L, Fenig M, Fields D, et al. Author details Emergency department use of apneic oxygenation versus usual care during 1 Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific rapid sequence intubation: a randomized controlled trial (the ENDAO trial). Institute, Via Olgettina 60, 20132 Milan, Italy. 2Università Vita-Salute San Acad Emerg Med. 2017;24:1387–94. Raffaele, Via Olgettina 58, 20132 Milan, Italy. 3Department of Anesthesia and 17. Sivilotti MLA, Ducharme J. Randomized, double-blind study on sedatives Intensive Care, Siberian Biomedical Research Center of the Ministry of Health, and hemodynamics during rapid-sequence intubation in the emergency Novosibirsk, Russia. 4Department of Cardiovascular Anesthesia and Intensive department: the SHRED study. Ann Emerg Med. 1998;31:313–24. Care, Cardiocentro Ticino, Lugano, Switzerland. 5Department of Surgery. 18. Pouraghaei M, Moharamzadeh P, Soleimanpour H, Rahmani F, Safari S, Discipline of Anesthesiology, Critical Care and Pain Medicine, Federal Mahmoodpoor A, et al. Comparison between the effects of alfentanil, University of São Paulo, São Paulo, Brazil. 6Department of Intensive Care fentanyl and sufentanil on hemodynamic indices during rapid sequence Cabrini et al. Critical Care (2018) 22:6 Page 9 of 9 intubation in the emergency department. Anesthesiol Pain Med. 2014;4: 40. 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