Dexmedetomidine for the management of awake fibreoptic intubation

  • Review
  • Intervention

Authors


Abstract

Background

Awake fibreoptic intubation (AFOI) frequently requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular function. The goal is to allow the patient to be responsive and co-operative. Medications such as fentanyl, remifentanil, midazolam and propofol have been reported to assist AFOI; however,these agents are associated with cardiovascular or respiratory adverse effects. Dexmedetomidine has been proposed as an alternative to facilitate AFOI.

Objectives

The primary objective of this review is to evaluate and compare the efficacy and safety of dexmedetomidine in the management of patients with a difficult or unstable airway undergoing awake fibreoptic intubation (AFOI).

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2012, Issue 5), MEDLINE (1966 to May 2012) through Ovid, EMBASE (1980 to May 2012) and Web of Science (1945 to May 2012); we screened the reference lists of all eligible trials and reviews to look for further trials and contacted authors of trials to ask for additional information. We searched for ongoing trials at http://www.controlledtrials.com/ and http://clinicaltrials.gov/ . We reran our search of all databases listed above on 21 November 2013.

Selection criteria

We included published and unpublished randomized controlled trials, regardless of blinding or language of publication, in participants 18 years of age or older who were scheduled for an elective AFOI because of an anticipated difficult airway. Participants received dexmedetomidine or control medications.

Data collection and analysis

Three review authors independently extracted data on study design, participants, interventions and outcomes. We assessed risk of bias using The Cochrane Collaboration’s tool. We estimated risk ratios (RRs) or mean differences (MDs) with 95% confidence internals (CIs) for outcomes with sufficient data; for other outcomes, we performed a qualitative analysis.

Main results

We identified four randomized controlled trials (RCTs), which included 211 participants. The four trials compared dexmedetomidine with midazolam, fentanyl, propofol or a sodium chloride placebo, respectively. The trials showed low or unclear risk of bias primarily because information provided on allocation concealment and other potential sources of bias was inadequate. Owing to clinical heterogeneity and potential methodological heterogeneity, it was impossible to conduct a full meta-analysis. We described findings from individual studies or presented them in tabular form. Limited evidence was available for assessment of the outcomes of interest for this review. Results of the limited included trials showed that dexmedetomidine significantly reduced participants' discomfort with no significant differences in airway obstruction, low oxygen levels or treatment-emergent cardiovascular adverse events noted during AFOI compared with control groups. When the search was rerun (from May 2012 to November 2013), it was noted that four studies are awaiting assessment. We will deal with these studies when we update the review.

Authors' conclusions

Small, limited trials provide weak evidence to support dexmedetomidine as an option for patients with an anticipated difficult airway who undergo AFOI. The findings of this review should be further corroborated by additional controlled investigations.

Résumé scientifique

La dexmédétomidine pour la prise en charge de l'intubation à fibre optique chez les patients éveillés

Contexte

L'intubation à fibre optique chez les patients éveillés (IFOE) nécessite fréquemment une sédation, un anxiolyse et un soulagement de la gêne, sans altérer la ventilation, ni perturber la fonction cardiovasculaire. L'objectif est de permettre au patient d'être sensible et coopératif. Il a été rapporté que certains médicaments, tels que le fentanyl, le rémifentanil, le midazolam et le propofol étaient utiles lors d'une IFOE; toutefois, ces agents sont associés à des effets respiratoires ou cardio-vasculaires indésirables. La dexmédétomidine a été proposée comme alternative pour faciliter l'IFOE.

Objectifs

L'objectif principal de cette revue est d'évaluer et de comparer l'efficacité et l'innocuité de la dexmédétomidine dans la prise en charge des patients ayant une respiration difficile ou instable et subissant une intubation à fibre optique en restant éveillé (IFOE).

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL ; 2012, numéro 5), MEDLINE (de 1966 à mai 2012) via Ovid, EMBASE (de 1980 à mai 2012) et Web of Science (de 1945 à mai 2012) ; nous avons passé au crible les références bibliographiques de tous les essais et de toutes les revues éligibles afin d'identifier d'autres essais et contacté les auteurs des essais pour obtenir des informations supplémentaires. Nous avons recherché des essais en cours au http://www.controlledtrials.com/ et http://clinicaltrials.gov/ . Nous avons recherché de nouveau toutes les bases de données mentionnées ci-dessus le 21 novembre 2013.

Critères de sélection

Nous avons inclus des essais contrôlés randomisés publiés et non publiés, indépendamment de la mise en aveugle ou de la langue de publication, chez des participants âgés de 18 ans ou plus qui devaient subir une IFOE élective en raison d'une respiration difficile anticipée. Les participants recevaient la dexmédétomidine ou des médicaments témoins.

Recueil et analyse des données

Trois auteurs de la revue ont indépendamment extrait les données du plan d'étude, des participants, des interventions et des critères de jugement. Nous avons évalué le risque de biais à l'aide de l'outil de la Collaboration Cochrane. Nous avons estimé les risques relatifs (RR) ou les différences moyennes (DM) avec un intervalle de confiance (IC) à 95% pour les critères de jugement avec suffisamment de données; pour les autres critères de jugement, nous avons effectué une analyse qualitative.

Résultats principaux

Nous avons identifié quatre essais contrôlés randomisés (ECR), qui incluaient 211 participants. Les quatre essais comparaient la dexmédétomidine avec le midazolam, le fentanyl, le propofol, le chlorure de sodium ou un placebo, respectivement. Les essais ont montré des risques de biais faibles ou incertains principalement parce que les informations sur l'assignation secrète et les autres sources potentielles de biais étaient inadéquates. En raison de l'hétérogénéité clinique et d'une hétérogénéité méthodologique potentielle, il était impossible de réaliser une méta-analyse. Nous avons décrit les résultats sous forme d'études individuelles ou de tableau. Des preuves limitées étaient disponibles pour évaluer les critères de jugement d'intérêt pour cette revue. Les résultats des essais limités inclus ont montré que la dexmédétomidine entraînait une réduction significative de l'inconfort des participants sans différence significative en termes d'obstruction des voies respiratoires, de faibles niveaux d'oxygène ou de traitement d'effets indésirables cardiovasculaires durant l'IFOE par rapport aux groupes témoins. Lorsque la recherche a été analysée de nouveau (de mai 2012 à novembre 2013), il a été noté que quatre études sont en attente d'évaluation. Nous les traiterons lorsque nous mettrons la revue à jour.

Conclusions des auteurs

Les essais limités, de petite taille, ne fournissent pas assez de preuves pour soutenir la dexmédétomidine comme une option chez les patients qui devaient subir une IFOE élective en raison d'une respiration difficile anticipée. Les résultats de cette revue doivent être confirmés par d'autres examens contrôlés randomisés supplémentaires.

Plain language summary

Is dexmedetomidine a good option for patients undergoing awake fibreoptic intubation?

This is a review of the clinical evidence from randomized controlled trials on the effect of dexmedetomidine in the management of awake fibreoptic intubation. The review was conducted by researchers in The Cochrane Collaboration. Awake fibreoptic intubation (AFOI) is indicated for the management of patients with a difficult or unstable (critical) airway, such as those with airway deformity or tumour, airway injury or spinal cord instability. It is necessary in such a situation to maintain patient co-operation and reduce patient anxiety without causing severe adverse effects during the AFOI. Many agents, including fentanyl, remifentanil, midazolam and propofol, have been reported to assist with AFOI. However, these agents can cause respiratory arrest, loss of airway control or reduced cardiovascular (heart) function, especially when used in high doses, thus increasing the risk of low oxygen levels (hypoxaemia), aspiration, low blood pressure (hypotension) or slow heart rate (bradycardia).

Dexmedetomidine is a selective alpha-2-adrenoceptor agonist that can cause sedation, anxiolysis, analgesic sparing, reduced salivary secretion and minimal respiratory depression; this might be beneficial for patients with a difficult or unstable airway undergoing AFOI.

We searched the medical literature until May 2012 and identified four randomized controlled trials involving 211 patients that were appropriate for inclusion in the review. These studies compared dexmedetomidine versus midazolam, fentanyl, propofol or a sodium chloride placebo for patients undergoing AFOI. We reran our search in November 2013, and four studies are awaiting assessment. We will deal with them when we update the review.

Dexmedetomidine significantly reduced patient discomfort during AFOI compared with control groups in two included trials. No significant differences in intubation time, airway obstruction, low oxygen levels or treatment-emergent cardiovascular adverse events were reported during AFOI between the dexmedetomidine group and the control group.

Dexmedetomidine did not appear to be inferior to other medications. The data from this evidence database of modest size provide limited evidence to support the use of dexmedetomidine as an alternative or primary choice for AFOI. Further research should focus on this important topic. Additional well-designed randomized controlled trials are needed to test the exact benefits of dexmedetomidine in the management of AFOI.

Résumé simplifié

Est-ce que la dexmédétomidine est une bonne option chez les patients subissant une intubation à fibre optique en restant éveillé ?

Ceci est une revue des données cliniques probantes issues d'essais contrôlés randomisés portant sur l'effet de la dexmédétomidine dans la prise en charge de l'intubation à fibre optique chez les patients éveillés. La revue a été effectuée par des chercheurs de la Collaboration Cochrane. L'intubation à fibre optique chez les patients éveillés (IFOE) est indiquée pour la prise en charge des patients ayant une respiration difficile ou instable (critique), tels que ceux atteints de difformité respiratoire ou de tumeur, de lésions au niveau des voies respiratoires ou d'instabilité de la moelle épinière. Dans une telle situation, il est nécessaire de maintenir la coopération des patients et de réduire leur anxiété sans entraîner d'effets indésirables graves au cours de l'IFOE. Il a été rapporté que de nombreux agents, y compris le fentanyl, le rémifentanil, le midazolam et le propofol étaient utiles lors d'une IFOE. Toutefois, ces agents peuvent entraîner un arrêt respiratoire, une perte du contrôle respiratoire ou une réduction de la fonction cardio-vasculaire (cSur), en particulier lorsqu'ils sont utilisés à doses élevées, accroissant le risque de faible niveau d'oxygène (hypoxie), d'aspiration, de faible pression artérielle (hypotension) ou de ralentissement du rythme cardiaque (bradycardie).

La dexmédétomidine est un agoniste sélectif des récepteurs alpha 2-adrénergiques qui peut entraîner une sédation, une anxiolyse, une analgésie limitée, une réduction de la sécrétion salivaire et une détresse respiratoire aiguë; cela pourrait être bénéfique chez les patients souffrant de respiration difficile ou instable et subissant une IFOE.

Nous avons effectué des recherches dans la littérature médicale jusqu'en mai 2012 et identifié quatre essais contrôlés randomisés portant sur 211 patients qui pouvaient être inclus dans la revue. Ces études comparaient le midazolam, le fentanyl, la dexmédétomidine par rapport à un placebo, au propofol ou au chlorure de sodium chez les patients subissant une IFOE. Nous avons réitéré notre recherche en novembre 2013 et quatre études sont en attente d'évaluation. Nous les traiterons lorsque nous mettrons la revue à jour.

Dans deux essais inclus, la dexmédétomidine réduisait significativement l'inconfort du patient pendant l'IFOE par rapport aux groupes témoins. Aucune différence significative en termes de temps d'intubation, d'obstruction des voies respiratoires, de faibles niveaux d'oxygène ou de traitement d'effets indésirables cardiovasculaires au cours de l'IFOE n'a été rapportée entre le groupe de dexmédétomidine et le groupe témoin.

La dexmédétomidine ne semblait pas être inférieure à d'autres médicaments. Les données issues de cette base de données de preuves de taille modeste fournissent des preuves limitées pour recommander l'utilisation de la dexmédétomidine, comme une méthode alternative ou privilégiée pour l'IFOE. De nouvelles recherches devraient se concentrer sur cet important sujet. D'autres essais contrôlés randomisés bien planifiés sont nécessaires pour tester les bénéfices exacts de la dexmédétomidine dans la prise en charge de l'IFOE.

Notes de traduction

Traduit par: French Cochrane Centre 15th June, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Background

Description of the condition

Awake fibreoptic intubation (AFOI) is indicated in a variety of clinical situations. An integral part of AFOI is the management of patients with a critical (difficult or unstable) airway, such as airway deformity or tumour, airway injury or spinal cord instability. An ideal situation for AFOI requires sedation, anxiolysis and relief of discomfort without impairing ventilation and depressing cardiovascular function, while allowing the patient to be responsive and co-operative. Many medications, such as fentanyl, remifentanil, midazolam and propofol, have been reported to assist AFOI (Knolle 2003; Lallo 2009; Machata 2003; Rai 2008). However, these agents can cause respiratory arrest, loss of airway control or cardiovascular depression, especially when used at high doses (Bergese 2007; Rai 2008). This increases the risk of hypoxaemia, aspiration, hypotension or bradycardia (Bailey 1990).

Description of the intervention

Dexmedetomidine is a selective alpha-2-adrenoceptor agonist with properties of sedation, anxiolysis, analgesic sparing and inhibition of salivary secretion (Gerlach 2007). The alpha-2/alpha-1-adrenoceptor selectivity ratio is eight-fold greater than for clonidine, the classic alpha-2-adrenoceptor agonist (Virtanen 1988). Dexmedetomidine has a half-life (t1/2) of approximately two hours, a duration of action of approximately four hours and a side effect profile that is shorter in duration than that of clonidine (i.e. much shorter influence on normal physiology).

When used at higher doses, dexmedetomidine exhibits minimal respiratory depression (Ebert 2000; Venn 2000). Thus dexmedetomidine has been proposed as a promising drug to use during AFOI for managing patients with a difficult or unstable airway (Hall 2000; Kamibayashi 2000). Dexmedetomidine has been approved for use in intubated and mechanically ventilated patients in the intensive care unit (ICU), as well as in non-intubated patients undergoing surgical or other procedures (Ebert 2000).

Although dexmedetomidine has beneficial attributes, increasing concentrations of dexmedetomidine in humans results in bradycardia and a biphasic (low, then high) dose-response relation for mean arterial pressure, especially in patients with intrinsic or drug-induced bradycardia, hypovolaemia, advanced heart block or severe ventricular dysfunction (Ebert 2000). It is recommended that dexmedetomidine be administered at a loading dose of 1 mcg/kg for at least 10 minutes, followed by a maintenance infusion of 0.2 to 0.5 mcg/kg/h.

How the intervention might work

Dexmedetomidine is pharmacologically unique in that the induced conscious sedation involves activation of the endogenous sleep-promoting pathway (Coursin 2001). Dexmedetomidine could provide sedation and anxiolysis via receptors within the locus coeruleus, which is an important modulator of wakefulness. Meanwhile, dexmedetomidine could provide analgesic sparing via receptors in the spinal cord and attenuation of the stress response with no significant respiratory depression (Gerlach 2007).

As an alpha-2-adrenoceptor agonist, dexmedetomidine when infused may lead to short-loop feedback inhibition of adrenaline (epinephrine) release from the adrenal gland. The clinical significance of this has yet to be determined.

Why it is important to do this review

The properties of dexmedetomidine may be beneficial for patients with a difficult or unstable airway undergoing AFOI when used as a sole infusion or as an adjuvant (Abdelmalak 2007; Maroof 2005). Case reports and studies have demonstrated the successful use of dexmedetomidine in AFOI (Bergese 2007; Grant 2004; Jooste 2005). On the other hand, dexmedetomidine has sympathetic modulating properties, which may be responsible for potential haemodynamic side effects, such as bradycardia, hypotension or conduction block, particularly in those who are hypovolaemic or bleeding or who have cardiac conduction or cardiac contractility limitations. It is important to perform a systematic review to assess the effectiveness of dexmedetomidine during AFOI and to document possible adverse effects or complications.

Objectives

The primary objective of this review is to evaluate and compare the efficacy and safety of dexmedetomidine in the management of patients with a difficult or unstable airway undergoing awake fibreoptic intubation (AFOI).

Methods

Criteria for considering studies for this review

Types of studies

We included published and unpublished randomized controlled trials, regardless of blinding or language of publication.

Types of participants

We included any patient older than 18 years of age who was scheduled for an elective AFOI because of an anticipated difficult airway.

Types of interventions

Dexmedetomidine versus any other control.

Types of outcome measures

Primary outcomes
  1. Discomfort during AFOI (heavy grimacing, verbal objection, defensive movement of head or hand or prolonged cough).

Secondary outcomes
  1. Intubation time.

  2. Airway obstruction (requiring neck extension or jaw retraction).

  3. Hypoxia (saturated peripheral oxygen (SpO2) < 90%).

  4. Treatment-emergent cardiovascular adverse events, mainly hypotension and bradycardia.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2012, issue 5) using the search terms detailed in Appendix 1; MEDLINE (1966 to May 2012) through Ovid; EMBASE (1980 to May 2012); and Web of Science (1945 to May 2012), using a similar strategy. (The search strategies will be found in Appendix 2; Appendix 3; and Appendix 4.) We combined the sensitive strategies described in Section 6.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) to search for randomized controlled trials (RCTs) in MEDLINE and EMBASE. We used the free text and associated exploded MeSH terms in combination with the RCT sensitive search strategy detailed in Appendix 5. We incorporated any identified new terms into the search strategy. We reported the modified search strategy in full in the final review.

We reran our search of all databases described above on 21 November 2013.

We applied no language restrictions.

Searching other resources

We screened the reference lists of all eligible trials and reviews.

We contacted experts to identify unpublished research and trials still under way. We searched for ongoing trials at http://www.controlledtrials.com/ and http://clinicaltrials.gov/ .

Data collection and analysis

Selection of studies

Using results of the above searches, we screened all titles and abstracts for eligibility. Two review authors (X-YH and J-PC) independently performed this screening. Each review author documented the reason for exclusion of each trial. We resolved disagreements by consulting with a third review author (X-YS), who decided on inclusion. In the case of insufficient published information available for decision making about inclusion, we contacted the first author of the relevant trial.

Data extraction and management

1. Extraction.

Two review authors (X-YH and J-PC) independently screened the titles and abstracts of search results for trial eligibility. We extracted and collected on a paper form the data from any trial that met our inclusion criteria. We noted the reasons for exclusions. We resolved disagreements by consulting with a third review author (X-YS), who decided on inclusion. If further information was required from the trial authors, X-YH would contact the first author of the relevant trial.

2. Management.
2.1 Conversion of ordinal to dichotomous outcome measures.

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinically significant response' or 'no clinically significant response'. It was generally assumed that if participants displayed heavy grimacing, verbal objection, defensive movement of head or hand or prolonged cough, this could be considered as clinically significant discomfort. Similarly, if participants required neck extension or jaw retraction, this could be considered a case of clinically significant airway obstruction.

Assessment of risk of bias in included studies

Two review authors (X-YH and J-PC) independently assessed the methodological quality of eligible trials. We resolved disagreements by discussion with a third review author (X-YS).

We performed the assessment as suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and by Juni (Juni 2001).

We considered a trial as having a low risk of bias if all of the following criteria were assessed as adequate. We considered a trial as having a high risk of bias if one or more of the following criteria were not assessed as adequate.

We assessed each trial according to the following quality domains.

  1. Random sequence generation: We considered allocation adequate if it was generated by a computer or by a random number table algorithm. We judged other processes as adequate, such as tossing of a coin, if the whole sequence was generated before the start of the trial, and if it was performed by a person not otherwise involved in participant recruitment. We considered allocation inadequate if a non-random system such as dates, names or identification numbers was used.

  2. Allocation concealment: We considered concealment adequate if the process used prevented participant recruiters, investigators and participants from knowing the intervention allocation of the next participant to be enrolled in the study. Acceptable systems included a central allocation system, sealed opaque envelopes and an on-site locked computer. We considered concealment inadequate if the allocation method that was used allowed participant recruiters, investigators or participants to know the treatment allocation of the next participant to be enrolled in the study (e.g. alternate medical record numbers, reference to case record numbers or date of birth, an open allocation sequence, unsealed envelopes).

  3. Blinding: We considered blinding adequate if participants and outcome assessors were each blinded to the intervention. We considered blinding inadequate if participants and outcome assessors were not blinded to the intervention.

  4. Intention-to-treat: We considered intention-to-treat (ITT) adequate if all dropouts or withdrawals were accounted for. We considered ITT inadequate if the number of dropouts or withdrawals was not stated, or if the reasons for dropouts or withdrawals were not stated.

We reported the 'Risk of bias' table as part of the table Characteristics of included studies and presented 'Risk of bias summary' figures (Figure 1 Figure 2, which detailed all judgements made for all studies included in the review.

Figure 1.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Measures of treatment effect

We presented dichotomous data as risk ratios. We presented numerical comparisons as differences between means.

Unit of analysis issues

The following were addressed: studies with multiple treatment groups. We combined all relevant experimental intervention groups of the study into a single group, and we combined all relevant control intervention groups into a single control group.

Dealing with missing data

We contacted the first author of included trials to try to obtain missing data. In the case of missing data, we used best case and worst case imputation of missing data. We ignored data that were missing at random, and we dealt with missing data not at random by using imputed data or statistical models.

Assessment of heterogeneity

1. Clinical heterogeneity.

We considered all included studies before determining clinical heterogeneity. We inspected all studies for outlying clinical situations or participants. When such situations or participant groups arose, we discussed them.

2. Methodological heterogeneity.

We considered all included studies initially before determining methodological heterogeneity. We inspected all studies for outlying methods. When methodological outliers arose, we discussed them clearly.

3. Statistical heterogeneity.

We assessed statistical heterogeneity with the I2 statistic, thereby estimating the percentage of total variance across studies that was due to heterogeneity rather than to chance alone (Higgins 2011). The importance of the observed value of I2 depended on:

  1. magnitude and direction of effects; and

  2. strength of evidence for heterogeneity (e.g. P value from the Chi2 test, or confidence interval (CI) for I2).

We considered a value of I2 greater than or equal to 50% accompanied by a statistically significant I2 statistic as evidence of substantial levels of heterogeneity, although we acknowledged that values of I2 ranging from 30% to 60% might also indicate substantial heterogeneity. When we found substantial levels of heterogeneity, we explored reasons for the heterogeneity. If strong heterogeneity was present (I2 ≥ 75%) and could not be explained by differences across trials in terms of clinical or methodological features, or by subgroup analyses, we did not combine the trials in a meta-analysis, but we presented the results in a forest plot.

Assessment of reporting biases

If more than 10 studies were included, we planned to assess publication bias and small-study effects in a qualitative manner, using a funnel plot. We planned to use arcsine asymmetry tests that stabilized the variance of binary outcomes (Rucker 2008).

Data synthesis

We intended to analyse data by using Review Manager software (RevMan 5.1) with a Mantel-Haenzsel fixed-effect model. This approach was intended to minimize the impact of small studies on the primary analysis of data, while addressing the issue of small-study effects. However, we were unable to implement these methods, as the appropriate data were not available in the included studies.

Subgroup analysis and investigation of heterogeneity

We performed no subgroup analyses.

Sensitivity analysis

We performed sensitivity analyses of trials with a low risk of bias versus a high risk of bias. We compared random-effects model and fixed-effect model estimates for each outcome variable. We excluded and included any study that appeared to have a large effect size (often the largest or earliest study) to assess its impact on the results of the meta-analysis. If large variations in the control group event rate were noted, we also subjected trials with different rates to sensitivity analysis.

Results

Description of studies

See Characteristics of included studies; Characteristics of excluded studies; and Characteristics of studies awaiting classification.

Results of the search

We identified six potentially eligible studies following screening of abstracts of potential studies. We found no ongoing trials and no trials awaiting assessment. The two review authors (X-YH and J-PC) completely agreed on the selection of included studies. We obtained no additional information from the primary authors. We reran our search on 21 November 2013, and four studies are awaiting assessment (Cattano 2012; Hu 2013; Li 2012; Qiu 2013). We will deal with these studies when we update the review.

Included studies

We included in this review four studies (Bergese 2010a; Bergese 2010b; Chu 2010; Tsai 2010) published between 2010 and May 2012. See Figure 3.

Figure 3.

Study flow diagram.

1. Methods.

All studies were started to be randomized and double-blinded. For further details, please see sections below on Allocation (selection bias) and Blinding (performance bias and detection bias).

2. Design.

All studies were randomized control trials and presented a parallel longitudinal design.

Bergese 2010a: This was a double-blinded (participant and assessor), randomized comparison study. Participants were randomly assigned (by computer-generated randomization schedule) to the midazolam (MDZ) group (n = 24) or the dexmedetomidine-midazolam (DEX-MDZ) group (n = 31) 15 minutes before fibreoptic intubation. MDZ participants received IV midazolam 0.05 mg/kg with additional doses at 0.05 mg/kg until their Ramsay Sedation Score (RSS) was ≥ 2. DEX-MDZ participants received midazolam 0.02 mg/kg followed by dexmedetomidine 1 μg/kg bolus infusion over 15 minutes. DEX-MDZ participants then received dexmedetomidine 0.1 to 0.7 μg/kg/h infusion until their RSS was ≥ 2. Topical local anaesthesia was performed with 2% lidocaine solution followed by a 4-mL injection of lidocaine 4% transtracheally. One of two trained, independent, study-blinded observers assessed participant reaction to the fibreoptic intubation on a scale of one to five (one = no reaction; two = slight grimacing; three = severe grimacing; four = verbal objection; and five = defensive movement of head, hands or feet).

Ramsay Sedation Scale (RSS: one to six): one: Participant is anxious and agitated or restless, or both; two: Participant is co-operative, oriented and tranquil; three: Participant responds to command only; four: Participant exhibits brisk response to light glabellar (between the eyebrows) tap or loud auditory stimulus; five: Participant exhibits a sluggish response to light glabellar tap or loud auditory stimulus; six: Participant exhibits no response to stimulus.

Bergese 2010b: This was a prospective, randomized, double-blind, placebo-controlled study. The study drug was started 15 minutes before airway topicalization for AFOI and was continued through intubation. Dexmedetomidine participants (n = 47) received a loading dose of 1.0 mcg/kg over 10 minutes followed by a continuous infusion of 0.7 mcg/kg-1/h-1. Placebo participants (n = 39) received a loading dose and a maintenance infusion of 0.9% sodium chloride for injection at a volume and rate equal to that of dexmedetomidine. Fifteen minutes after the start of the study drug infusion and before airway topicalization, the participant's level of sedation was assessed using the RSS. Any participant rated as < two on this scale was given rescue midazolam in 0.5-mg bolus doses until RSS ≥ two was attained. Airway anaesthesia was achieved using lidocaine via aerosol, spray, topical jelly, gargle and/or nerve blocks. Study drug infusion was stopped upon completion of the AFOI. All adverse effects and concomitant medications were recorded.

Chu 2010: This was a randomized controlled study. Participants in the Dex group (n = 16) received dexmedetomidine infusion, while the control group (n = 14) received fentanyl infusion. Each participant was given a loading dose of dexmedetomidine (1.0 μg/kg-1) or fentanyl (1.0 μg/kg-1) for 10 minutes. After the middle of infusion, topical anaesthesia was performed: Bilateral inferior nasal canals were packed with 6% cocaine (60 mg), and the tongue and the hypopharynx were then sprayed with 10% lidocaine (60 mg). Two experienced consultant anaesthetists performed airway management. While one consultant performed AFOI, another consultant controlled the drug infusion and recorded anaesthetic data. Immediately at the end of study drug infusion, the consultant started to perform fibreoptic scope. The consultant who performed AFOI, the participants and the postoperative recorder were blinded to each participant's group. Main outcomes measures were nasal intubation score (one: no movement; two: grimacing; three: mild cough; four: major limb movement; five: prolonged cough). Secondary outcomes included consumption time from insertion of fibreoptic scope to confirmation of nasal tracheal intubation, hypoxic episode (SpO2 < 95%) and the use of atropine or ephedrine for haemodynamic support.

Tsai 2010: This was a randomized controlled study. Participants in the Dex group (n = 20) received a loading dose of dexmedetomidine (1.0 μg/kg-1) infused over 10 minutes. Participants in the propofol group (n = 20) received propofol administered by a Primea TCI pump (Fresenius Kabi, Brezins, France). The initial target effect site concentration (Ce) was set at 3 μg/mL-1 and was adjusted by 1.0 μg/mL-1 according to participant comfort during the procedure. While waiting for the desired level of sedation to be achieved, topical anaesthesia was applied to the airway. Cocaine 6% (60 mg) packs were applied bilaterally to the inferior nasal canals; then, the tongue and the hypopharynx were sprayed with lidocaine 10% (60 mg). Fibreoptic intubation was performed once the dexmedetomidine infusion had ended, or when the propofol infusion target concentration at the effect site (Ce) had equilibrated with the plasma concentration (Cp). Two experienced consultant anaesthetists performed airway management. While one anaesthetist performed fibreoptic intubation, the other anaesthetist controlled the drug infusion. Anaesthetic data and postoperative visits were documented by a study nurse. The intubating anaesthetist, participants and the study nurse who recorded details of the procedures were all blinded to the study. The primary outcome measurements were participant tolerance, as assessed by a five-point fibreoptic intubation comfort score (one: no reaction; two: slight grimacing; three: heavy grimacing; four: verbal objection; five: defensive movement of head or hands). Other parameters assessed in relation to awake fibreoptic intubation included an airway obstruction score (one: patent airway; two: airway obstruction relieved by neck extension; three: airway obstruction requiring jaw retraction); intubation time (time from insertion of the fibreoptic scope to confirmation of nasotracheal intubation); any hypoxic episode (SpO2 < 90%); and the need for atropine or adrenaline administration. 

3. Duration.

Three studies (Bergese 2010a; Chu 2010; Tsai 2010) were of short duration (less than two days), but one (Bergese 2010b) had a follow-up period of 30 days.

4. Participants.

The total number of included participants was 211. All participants were 18 years of age and older and were scheduled for an elective AFOI because of an anticipated difficult airway.

5. Setting.

All studies were conducted in a hospital setting. Two studies (Bergese 2010a; Bergese 2010b) were conducted in the USA, and the remaining two studies (Chu 2010; Tsai 2010) were conducted in Taiwan.

6. Interventions.

Dexmedetomidine was compared with no treatment in one study (Bergese 2010b), with propofol in one study (Tsai 2010) and with fentanyl in one study (Chu 2010). In addition, dexmedetomidine with midazolam was compared with midazolam only in one study (Bergese 2010a).

7.Outcomes.

The primary outcome "Discomfort during awake fibreoptic intubation" was not presented in raw data in two studies (Chu 2010; Tsai 2010); this made it impossible to extract data for synthesis, so we contacted the first author of the relevant study and obtained details of the raw data (Table 1; Table 2). Other outcomes were expressed by numerical data or ordinal data.

Table 1. Raw data for Chu 2010
FOI comfort (1, 2, 3, 4, 5) Dexmedetomidine Fentanyl
160
252
357
404
501
Table 2. Raw data for Tsai 2010
FOI comfort (1, 2, 3, 4, 5) Dexmedetomidine Propofol
170
299
336
413
502

Excluded studies

The review excluded two studies published between 2010 and 2012 (Boyd 2011; Swaniker 2011).

Risk of bias in included studies

We used The Cochrane Collaboration's risk of bias tables to assess the validity and quality of the included trials. The trials showed low or unclear risk of bias primarily because of inadequate information on allocation concealment and other potential sources of bias. For a more detailed description of individual trial qualities, see the table Characteristics of included studies. The various bias domains are presented in the 'Risk of bias graph' and in a 'Risk of bias summary' (Figure 1; Figure 2).

Allocation

All studies were unclear about allocation concealment. One study (Tsai 2010) was not explicit about how allocation was achieved other than using the phrase "randomly allocated".

Blinding

All studies were conducted on a double-blind basis. One study (Bergese 2010b) did not explicitly describe how this was undertaken. We have, however, rated the other three studies as being of higher quality because they stated that the studies were double-blinded and specifically that either the raters or the participants were blinded.

Incomplete outcome data

In all studies, every person who completed the trial was analysed.

Selective reporting

The data in this review originated from published papers. We did not have an opportunity to compare outcomes described in the protocol and those reported in the full publications. So we considered selective reporting possible. One study (Bergese 2010a) did not provide data on our secondary outcome "Intubation time", and another study (Bergese 2010b) did not provide data on our primary outcome "Discomfort during awake fibreoptic intubation" and the secondary outcome "Intubation time".

Other potential sources of bias

All studies had small or very small sample sizes. Two studies (Bergese 2010a; Bergese 2010b) were funded by Hospira, the maker of dexmedetomidine.

Effects of interventions

Owing to clinical heterogeneity and potential methodological heterogeneity, it was impossible to conduct a full meta-analysis. We described findings from individual studies or presented them in tabular form.

Primary outcomes

1, Discomfort during awake fibreoptic intubation (heavy grimacing, verbal objection, defensive movement of head or hand or prolonged cough).

This outcome was reported in three studies involving 125 participants (Bergese 2010a; Chu 2010; Tsai 2010; Table 3). In two studies, participants experienced less discomfort during awake fibreoptic intubation in the dexmedetomidine group than in the control group (Bergese 2010a; Tsai 2010). However, in Chu 2010, no significant difference was reported between the dexmedetomidine group and the control group. This outcome was not reported in Bergese 2010b.

Table 3. Table 1
Primary outcome Discomfort during awake fibreoptic intubation
Bergese 2010aDexmedetomidine group reacted less (P < 0.001)
Bergese 2010bNot reported
Chu 2010No significant difference between groups
Tsai 2010Dexmedetomidine group reacted less (P < 0.05)

Secondary outcomes

1. Intubation time.

Only two studies (Chu 2010; Tsai 2010; Table 4) involving 70 participants reported on this outcome, both showing no significant difference between the dexmedetomidine group and the control group.

Table 4. Table 2
Secondary outcome Intubation time Airway obstruction Hypoxia Treatment-emergent cardiovascular adverse events
Bergese 2010aNot reportedNot clearly reportedNo significant difference between groupsNo significant difference between groups
Bergese 2010bNot reportedNot clearly reportedNo significant difference between groupsNo significant difference between groups
Chu 2010No significant difference between groupsNo significant difference between groupsNo significant difference between groupsNo significant difference between groups
Tsai 2010No significant difference between groupsNo significant difference between groupsNo significant difference between groupsNo significant difference between groups
2. Airway obstruction (requiring neck extension or jaw retraction).

This outcome was reported clearly in two studies involving 70 participants (Chu 2010; Tsai 2010; Table 4). Tsai 2010 showed that dexmedetomidine alleviated airway obstruction significantly (P value 0.007), and Chu 2010 showed no significant difference between the dexmedetomidine group and the control group.

3. Hypoxia (saturated peripheral oxygen (SpO2) < 90%).

This outcome was reported in four studies involving 211 participants (Bergese 2010a; Bergese 2010b; Chu 2010; Tsai 2010; Table 4). Bergese 2010a reported no complications in either group, and none of the DEX-MDZ participants experienced respiratory depression. Bergese 2010b showed that dexmedetomidine had no significant effect on respiratory function and gas exchange at the doses used in this trial. Tsai 2010 showed no significant difference between the dexmedetomidine group and the control group. Chu 2010 reported no episode of apnoea or decreased oxygen saturation less than 95% in both groups.

4. Treatment-emergent cardiovascular adverse events, mainly hypotension and bradycardia.

This outcome was reported in four studies involving 211 participants (Bergese 2010a; Bergese 2010b; Chu 2010; Tsai 2010; Table 4). Bergese 2010a showed no significant haemodynamic difference between the two subject groups. Bergese 2010b reported that seven dexmedetomidine-treated participants and four placebo-treated participants received an intravenous fluid bolus or medication to treat blood pressure or heart rate (HR) during study drug infusion. The difference was insignificant. Both Tsai 2010 and Chu 2010 showed that haemodynamic support did not differ significantly between the dexmedetomidine group and the control group.

Discussion

Summary of main results

The research on dexmedetomidine for the management of awake fibreoptic intubation has started only within the past few years, so in this review, only four studies involving 211 participants were included (Bergese 2010a; Bergese 2010b; Chu 2010; Tsai 2010). It is true that some outcomes of interest for this review were not reported in these studies. The analytic results were derived from sparse data.

Dexmedetomidine-treated participants reacted less than control-treated participants to awake fibreoptic intubation in two trials (Bergese 2010a; Tsai 2010). The decreased discomfort achieved with dexmedetomidine favours maintaining patient co-operation and reducing anxiety during AFOI and could play an important role in securing the airway of patients with an unstable cervical spine or a compromised spinal cord.

No suggestion indicates that dexmedetomidine had a greater effect on intubation time than was seen with the control. Dexmedetomidine does not predispose to airway obstruction and respiratory depression. Airway obstruction occurred more frequently in the propofol group than in the dexmedetomidine group. The incidence of hypoxia was similar between the dexmedetomidine group and the control group and was clinically insignificant. Treatment-emergent cardiovascular adverse events, mainly hypotension and bradycardia, were reported in some studies for the dexmedetomidine group and for the control group as well. Most adverse effects were mild or moderate in severity and could be easily managed with atropine, ephedrine and intravenous fluid administration. The results of this review do not suggest that dexmedetomidine causes significantly more cardiovascular adverse events.

Overall completeness and applicability of evidence

No outcomes in this review involved large numbers of participants. The primary outcome "Discomfort during awake fibreoptic intubation" was not reported in one study (Bergese 2010b). All studies were performed in hospital settings, and all included participants were anticipated to have a difficult or unstable airway. The intervention dexmedetomidine is readily accessible, and the outcomes are objective in terms of clinical practice. Dexmedetomidine had important effects, so the findings might well be applicable.

Quality of the evidence

The largest study in this area (Bergese 2010b) was a multicentre (17 medical centres) study that included 86 participants between August 7, 2006, and January 26, 2007. It is impossible to detect subtle yet important differences due to dexmedetomidine with any confidence. Although the four studies are all RCTs without high risk of bias, the overall quality of reporting of these studies was very low because allocation concealment was not described and other bias could not be excluded. In addition, the small study size and the poor reporting of studies would be associated with an exaggeration of effect of the experimental treatment if an effect had been detected (Juni 2001). Comparisons were performed between dexmedetomidine and any control (including sodium chloride, fentanyl, midazolam and propofol) in the four different studies included in this review. In consideration of the clinical heterogeneity and the likely methodological heterogeneity (measurement of outcomes) that might cause a negative influence in the quality of evidence, we did not perform a full meta-analysis instead of a narrative analysis (Table 5).

Table 5. Results of included studies
Study Interventions Outcomes Main results
Bergese 2010a

MDZ group (n = 24): Participants received IV midazolam 0.05 mg/kg with additional doses to achieve a Ramsay Sedation Scale (RSS) score ≥ two

DEX-MDZ group (n = 31): Participants received midazolam 0.02 mg/kg followed by dexmedetomidine 1 μg/kg, then an infusion of dexmedetomidine 0.1 μg/kg/h and titrated to 0.7 μg/kg/h to achieve RSS ≥ two

Topical local anaesthetics were given

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no reaction; two: slight grimacing; three: severe grimacing; four: verbal objection; five: defensive movement of head, hands or feet)

Airway obstruction (no details)

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

DEX-MDZ participants reacted less to AFOI than did MDZ participants (P < 0.01)

No complications were reported in either participant group, and none of the 31 DEX-MDZ participants experienced respiratory depression

Bergese 2010b

Dexmedetomidine (n = 47): Participants received a loading dose of 1.0 mcg/kg over 10 minutes, followed by a continuous infusion of 0.7 mcg/kg-1/h-1. The study drug was started 15 minutes before airway topicalization for AFOI

Placebo group (n = 39): Participants received a loading dose and a maintenance infusion of 0.9% sodium chloride for injection at a volume and rate equal to that of dexmedetomidine. Fifteen minutes after the start of the study drug infusion and before airway topicalization, any participant with Ramsay Sedation Scale < two received rescue midazolam to achieve targeted sedation (RSS >= two) before topicalization and throughout AFOI

Airway obstruction

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

Dexmedetomidine has no significant effect on respiratory function and gas exchange at the doses used in this trial. Dexmedetomidine is well tolerated and does not compromise the airway

Seven dexmedetomidine-treated participants (12.7%) and four placebo-treated participants (8.0%) received intravenous fluid bolus or medication to treat blood pressure or HR during study drug infusion

Chu 2010

Dex group (n = 16): Participants received dexmedetomidine (1.0 μg/kg-1) infusion

Control group (n = 14): Participants received fentanyl (1.0 μg/kg-1) infusion

Topical anaesthesia was performed after the middle of infusion

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no movement; two: grimacing; three: mild cough; four: major limb movement; five: prolonged cough)

Intubation time (from insertion of fibreoptic scope to confirmation of nasal tracheal intubation)

Airway obstruction (Participants were assessed on a scale of one to three: one: patent airway; two: airway obstruction relieved by neck extension; three: airway obstruction requiring jaw retraction)

Hypoxia (SpO2 < 94%)

Treatment-emergent cardiovascular adverse events

No differences between the two groups were noted for discomfort during awake fibreoptic intubation, intubation time, airway obstruction, hypoxia or treatment-emergent cardiovascular adverse events
Tsai 2010

Dexmedetomidine group (n = 20): Participants received a loading dose of dexmedetomidine (1.0 μg/kg-1) infused over 10 minutes

Propofol group (n = 20): Participants received propofol. The initial target effect site concentration (Ce) was set at 3 μg/mL-1. This was adjusted by 1.0 μg/mL-1 according to participant comfort during the procedure. If a comfort score exceeded three or a persistent cough occurred during the procedure, the TCI was titrated upwards, after which the intubating anaesthetist waited for 60 seconds before proceeding. While waiting for the desired level of sedation to be achieved, topical anaesthesia was applied to the airway

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no reaction; two: slight grimacing; three: heavy grimacing; four: verbal objection; five: defensive movement of head or hands)

Intubation time (time taken from insertion of the fibreoptic scope to confirmation of nasotracheal intubation)

Airway obstruction (Participants were assessed on a scale of one to three: one: patent airway; two: airway obstruction relieved by neck extension; three: airway obstruction requiring jaw retraction)

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

DEX participants reacted less to AFOI than did the propofol participants (P < 0.01)

No differences between the two groups were noted for intubation time or hypoxia

The dexmedetomidine group experienced fewer airway events and less heart rate response than did the propofol group (P < 0.003 and P value 0.007,respectively)

Potential biases in the review process

1. Missing studies.

Although we have tried our best to identify all relevant studies, it is possible that some small studies are missing from this review. However, because of the comprehensive searching strategy provided by Karen Hovhannisyan (Cochrane Anaesthesia Review Group Trials Search Co-ordinator), we are confident that we have not failed to identify large relevant studies.

Agreements and disagreements with other studies or reviews

No previous Cochrane review or relevant systemic review was performed.

Authors' conclusions

Implications for practice

1. For patients.

In the patient with an at-risk cervical spine or a difficult airway, it is frequently necessary to maintain patient co-operation and to reduce anxiety without causing severe adverse effects during AFOI. The pharmacological properties of dexmedetomidine perhaps make it a promising drug in securing the airway and providing better tolerance for patients during AFOI.

2. For clinicians.

When performing AFOI, anaesthesiologists may find it difficult to provide enough sedation for patients to be comfortable and co-operative, while at the same time avoiding airway compromise from excessive sedation. Current clinical data show that dexmedetomidine is an effective alternative for patients with high-risk airways undergoing AFOI and may provide more comfort and less airway obstruction. Comparable temporary haemodynamic adverse effects were noted in the dexmedetomidine-treated group when compared with controls (Bergese 2010b; Chu 2010; Tsai 2010).

3. For policy makers or managers.

Dexmedetomidine might be considered as another option for patients with an anticipated difficult airway undergoing AFOI.

Implications for research

All four included studies mentioned how investigators calculated the sample size. However, studies involving a larger sample size would provide more precise estimates of effects. In addition, the power of this review would have been enhanced by better reporting of data. For example, all included studies did not explicitly state information about "allocation concealment". Overall, the included studies were limited, and additional well-designed randomized controlled trials are needed to test the exact effects of dexmedetomidine in the management of patients who require awake fibreoptic intubation.

Acknowledgements

We would like to thank Jane Cracknell (Cochrane Anaesthesia Review Group (CARG) Managing Editor), Karen Hovhannisyan (CARG Trials Search Co-ordinator), Mark Neuman (content editor), Basem Abdelmalak (peer reviewer), Douglas Coursin (peer reviewer), Janet Wale (consumer editor) and Nathan Pace (statistical editor) for their help and editorial advice during the preparation of this systematic review.

Data and analyses

Download statistical data

This review has no analyses.

Appendices

Appendix 1. CENTRAL search strategy

#1 Mesh descriptor Dexmedetomidine explore all trees

#2 Mesh descriptor Optical fibers explore all trees

#3 (fibre or fiber) near optic

#4 #2 or #3

#5 #1 and #4

Appendix 2. Ovid MEDLINE search strategy

#1 exp Dexmedetomidine/ or dexmedetomidine.af.

#2 ((randomised controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (animals not (humans and animals)).sh.

#3 1 and 2

Appendix 3. Ovid EMBASE search strategy

#1 exp dexmedetomidine/ OR dexmedetomidine.ti,ab.

#2 (placebo.sh. or controlled study.ab. or random*.ti,ab. or trial*.ti,ab. or ((singl* or doubl* or trebl* or tripl*) adj3 (blind* or mask*)).ti,ab) not (animals.sh not (humans.sh and animals.sh))

#3 #1 and #2

Appendix 4. Web of Science search

#1.TS=dexmetetomidine

#2. TS=fibreoptic or fibreoptic

#3. #1 and #2

Appendix 5. Free text terms and associated explored MeSH terms

#1 Research design

#2 Randomization

#3 Random Allocation

#4 Clinical Trials, Randomized

#5 Controlled Clinical Trials, Randomized

#6 Trials, Randomized Clinical

#7 Randomized Controlled Trial

#8 Double-Blind Method

#9 Double-Blind Study

#10 Single-Blind Method

#11 Single-Blind Study

Contributions of authors

Conceiving of the review: X-YH, J-PC, X-YS

Co-ordinating the review:

Undertaking manual searches: X-YH, J-PC, X-YS

Screening search results: X-YH, J-PC, X-YS

Organizing retrieval of papers: X-YH, J-PC, X-YS

Screening retrieved papers against inclusion criteria: X-YH, J-PC, X-YS

Appraising quality of papers: X-YH, J-PC, X-YS

Abstracting data from papers: X-YH, J-PC, X-YS

Writing to authors of papers for additional information: X-YH

Providing additional data about papers: X-YH

Obtaining and screening data on unpublished studies: X-YH, J-PC, X-YS

Providing data management for the review: X-YH, J-PC, X-YS

Performing other statistical analysis not using RevMan: QH

Interpreting data: QH

Making statistical inferences: QH

Writing the review: X-YH, J-PC, X-YS

Securing funding for the review: X-YH

Performing previous work that was the foundation of the present study: none

Serving as guarantor for the review (one author): X-YS

Taking responsibility for reading and checking the review before submission: X-YH, J-PC, X-YS, QH

Declarations of interest

None known.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Natural Scientific Foundation of China (81100049), China.

Differences between protocol and review

We have changed the title of the published protocol (He 2012) from "Dexmedetomidine for the management of fibreoptic intubation" to "Dexmedetomidine for the management of awake fibreoptic intubation". A new author, J-P Cao, is involved in writing the review. In addition, we included only four eligible RCTs for this review, so we referred to dexmedetomidine versus any control instead of the "types of interventions" mentioned in our protocol.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bergese 2010a

Methods

Design: randomized, double-blinded study

Setting: academic medical centre

Participants55 ASA physical status I, II, III and IV patients, aged 18 to 85 years, scheduled for non-emergency surgery with AFOI
Interventions

MDZ group (n = 24): Participants received IV midazolam 0.05 mg/kg with additional doses to achieve a Ramsay Sedation Scale (RSS) score of ≥ two

DEX-MDZ group (n = 31): Participants received midazolam 0.02 mg/kg followed by dexmedetomidine 1 μg/kg, then an infusion of dexmedetomidine 0.1 μg/kg/h and titrated to 0.7 μg/kg/h to achieve RSS ≥ two

Topical local anaesthetics were given

Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no reaction; two: slight grimacing; three: severe grimacing; four: verbal objection; five: defensive movement of head, hands or feet)

Airway obstruction (no details)

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'. It was generally assumed that if participants displayed heavy grimacing, verbal objection, defensive movement of head, hands or feet or prolonged cough, this could be considered as clinically significant discomfort

One of two trained, independent, study-blinded observers assessed participant discomfort during placement of the fibreoptic scope

No definition was provided for "airway obstruction", "hypoxia" or "treatment-emergent cardiovascular adverse events", but the study author mentioned in the Discussion section, "There were no complications reported in either patient group, and none of the 31 DEX-MDZ patients experienced any respiratory depression"

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomization schedule
Allocation concealment (selection bias)Unclear riskNo details
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts
Selective reporting (reporting bias)Unclear riskNot all expected outcomes reported
Other biasUnclear riskSmall sample size
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded (participant and assessor)
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded (participant and assessor)

Bergese 2010b

Methods

Design: randomized, double-blinded, placebo-controlled study

Setting: 17 medical centres in the United States

Participants

All adult patients undergoing AFOI for non-emergency surgery were potential candidates for this study. Patients were excluded from this study if they were:

  1. prisoners;

  2. pregnant;

  3. mentally ill;

  4. younger than 18 years of age;

  5. known or admitted alcohol or drug abusers; or

  6. allergic to the drugs involved in the study

Interventions

Dexmedetomidine group (n = 47): Participants received a loading dose of 1.0 mcg/kg over 10 minutes followed by a continuous infusion of 0.7 mcg/kg-1/h-1.The study drug was started 15 minutes before airway topicalization for AFOI

Placebo group (n = 39): Participants received a loading dose and a maintenance infusion of 0.9% sodium chloride for injection at a volume and rate equal to those of dexmedetomidine. Fifteen minutes after the start of study drug infusion and before airway topicalization, any participant with Ramsay Sedation Scale < two received rescue midazolam to achieve targeted sedation (RSS ≥ two) before topicalization and throughout AFOI

Outcomes

Airway obstruction

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

Notes

RSS (Ramsay Sedation Scale: one to six): 1: Participant is anxious and agitated or restless, or both; 2: Participant is cooperative, oriented and tranquil; three: Participant responds to command only; four: Participant exhibits brisk response to light glabellar (between the eyebrows) tap or loud auditory stimulus; five: Participant exhibits a sluggish response to light glabellar tap or loud auditory stimulus; six: Participant exhibits no response to stimulus

No definition was provided for "airway obstruction" or "hypoxia", but the study author mentioned in the Discussion that "Dexmedetomidine has no significant effect on respiratory function and gas exchange at the doses used in this trial"

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskParticipants were randomly assigned 1:1 to receive dexmedetomidine or placebo. No further details
Allocation concealment (selection bias)Unclear riskNo details
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts
Selective reporting (reporting bias)Unclear riskNot all expected outcomes reported
Other biasUnclear riskSmall sample size
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded

Chu 2010

Methods

Design: randomized study. The intubating anaesthetist, participants and recorders were all blinded to each participant's group

Setting: academic medical centre

ParticipantsWe enrolled 30 oral cancer patients with limited mouth opening who were undergoing AFOI for elective surgery
Interventions

Dex group (n = 16): Participants received dexmedetomidine (1.0 μg/kg-1) infusion

Control group (n = 14): Participants received fentanyl (1.0 μg/kg-1) infusion

Topical anaesthesia was performed after the middle of infusion

Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no movement; two: grimacing; three: mild cough; four: major limb movement; five: prolonged cough)

Intubation time (from insertion of fibreoptic scope to confirmation of nasal tracheal intubation)

Airway obstruction (Participants were assessed on a scale of one to three: one: patent airway; two: airway obstruction relieved by neck extension; three: airway obstruction requiring jaw retraction)

Hypoxia (SpO2 < 94%)

Treatment-emergent cardiovascular adverse events

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'

It was generally assumed that if participants displayed heavy grimacing, verbal objection, defensive movement of head, hands or feet or prolonged cough, this could be considered as clinically significant discomfort. If participants required neck extension or jaw retraction, it could be considered as clinical significant airway obstruction

Two participants developed bradycardia (lowest heart rates were 48 and 45 beat/min), and one developed hypotension (78/46 mmHg) in the Dex group. No profound bradycardia (heart rate <40 beats/min) occurred in each group

Two experienced consultant anaesthetists certified in advanced airway life support performed airway management for all study participants

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskParticipants were allocated randomly to one of two groups via a computer-generated random number table
Allocation concealment (selection bias)Unclear riskNo details
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts
Selective reporting (reporting bias)Low riskAll expected outcomes reported
Other biasUnclear riskSmall sample size
Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe consultant who performed AFOI, the participants and the postoperative recorder were all blinded to each participant's group
Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe consultant who performed AFOI, the participants and the postoperative recorder were all blinded to each participant's group

Tsai 2010

Methods

Design: randomized study. The intubating anaesthetist, participants and the study nurse who recorded details of the procedures were all blinded to the study

Setting: academic medical centre

ParticipantsForty participants with anticipated difficult airways and due to undergo tracheal intubation for elective surgery were enrolled
Interventions

Dexmedetomidine group (n = 20): Participants received a loading dose of dexmedetomidine (1.0 μg/kg-1) infused over 10 minutes

Propofol group (n = 20): Participants received propofol. The initial target effect site concentration (Ce) was set at 3 μg/mL-1. This was adjusted by 1.0 μg/mL-1 according to participant comfort during the procedure. If a comfort score exceeded three or a persistent cough occurred during the procedure, the TCI was titrated upwards, after which the intubating anaesthetist waited for 60 s before proceeding. While waiting for the desired level of sedation to be achieved, topical anaesthesia was applied to the airway

Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no reaction; two: slight grimacing; three: heavy grimacing; four: verbal objection; five: defensive movement of head or hands)

Intubation time (time taken from insertion of the fibreoptic scope to confirmation of nasotracheal intubation)

Airway obstruction (Participants were assessed on a scale of one to three: one: patent airway; two: airway obstruction relieved by neck extension; three: airway obstruction requiring jaw retraction)

Hypoxia (no details)

Treatment-emergent cardiovascular adverse events (no details)

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'

It was generally assumed that if participants displayed heavy grimacing, verbal objection, defensive movement of head, hands or feet or prolonged cough, this could be considered as clinically significant discomfort. If participants required neck extension or jaw retraction, this could be considered as clinically significant airway obstruction

No obvious definition was provided for "airway obstruction" or "hypoxia"

Two experienced consultant anaesthetists certified in advanced airway life support performed airway management for all study participants

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskParticipants were randomly allocated. No further details
Allocation concealment (selection bias)Unclear riskNo details
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts
Selective reporting (reporting bias)Low riskAll expected outcomes reported
Other biasUnclear riskSmall sample size
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Boyd 2011Three case reports
Swaniker 2011None of the outcomes were reported

Characteristics of studies awaiting assessment [ordered by study ID]

Cattano 2012

Methods

Design: randomized, double-blinded study

Setting: a hospital affiliated with the Universtiy medical school

Participants34 adult ASA I to III participants who required AFOI. Because of case cancellations or delays, only 30 participants were included
InterventionsParticipants were randomly assigned by the pharmacy to one of two groups: group REM (remifentanil) and group DEX (dexmedetomidine). All participants received a loading dose at a rate of 0.1 mL/kg over 10 minutes and a continuous infusion at a rate of 0.1 mL/kg/h of their respective drug. Participants in group REM received a remifentanil loading dose of 0.75 mcg/kg, and participants in group DEX received a dexmedetomidine loading dose of 0.4 mcg/kg over 10 minutes. The continuous infusion was begun with participants
in group REM receiving remifentanil at 0.075 mcg/kg/min and those in group DEX receiving dexmedetomidine at 0.7 mcg/kg/h
Outcomes

Airway obstruction (no details)

Hypoxia

Treatment-emergent cardiovascular adverse events

NotesNo definition was provided for "airway obstruction", "hypoxia" or "treatment-emergent cardiovascular adverse events", but the study author provided the details in "Results---Table 4"

Hu 2013

Methods

Design: randomized, double-blinded study

Setting: a hospital affiliated with the Universtiy medical school

ParticipantsForty-two adult patients with American Society of Anesthesiologists (ASA) classifications of I to III were recruited for elective awake fibreoptic nasotracheal intubation following diagnosis of maxillofacial cancer or fracture with limited mouth opening. One patient declined consent, and one operation was cancelled
InterventionsForty participants undergoing elective awake fibreoptic nasotracheal intubation were allocated randomly to receive either dexmedetomidine (n = 20) or remifentanil (n = 20). Participants in the dexmedetomidine group received a loading dose (1.5 μg/kg) infused over 10 minutes followed by a continuous infusion of 0.7 μg/kg/h. Participants in the remifentanil group received remifentanil via an Orchestra Base Primea (Fresenius Vial) infusion system using a Minto pharmacokinetic model. The initial target was 3.0 ng/mL, and the TCI was adjusted by 0.5 ng/mL after the target concentration at the effect site had equilibrated with the plasma concentration until the desired level of sedation was achieved
Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: grimacing; two: localizing; three: coughing on lidocaine via scope; four: coughing on entering infraglottic space; five: prolonged coughing)

Intubation time (from insertion of fibreoptic scope to confirmation of nasal tracheal intubation)

Airway obstruction (no details)

Hypoxia

Treatment-emergent cardiovascular adverse events

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'

It was generally assumed that if participants displayed coughing on lidocaine via scope or on entering infraglottic space or prolonged cough, this could be considered as clinically significant discomfort

No definition was provided for "airway obstruction" or "hypoxia"

Two consultant anaesthetists were present during all procedures. One was responsible for performing the awake nasal fibreoptic intubation and scoring sedation, endoscopy, intubation and postintubation conditions; the other administered the study drugs. An anaesthetist nurse collected anaesthetic data and postoperative records. The intubating anaesthetist, the participants and the nurse anaesthetist were all blinded to the study drugs used

Li 2012

Methods

Design: randomized, double-blinded study

Setting: a hospital affiliated with the Universtiy medical school

ParticipantsThirty participants with an anticipated difficult airway caused by huge goitre were enrolled and randomly divided into dexmedetomidine group (n = 15) and propofol group (n = 15)
InterventionsParticipants in the dexmedetomidine group received a loading dose of dexmedetomidine (1.0 μg/kg-1), infused over 10 minutes, then pumped at a continuous rate of 0.4 μg/kg -1/h-1. Participants in the propofol group received a loading dose of 2.0 mg/kg-1 pumped at a continuous rate of 5 to 8 mg/kg-1/h-1
Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no reaction; two: slight grimacing; three: severe grimacing; four: verbal objection; five: defensive movement of head, hands or feet)

Airway obstruction

Hypoxia

Treatment-emergent cardiovascular adverse events

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'. It was generally assumed that if participants displayed heavy grimacing, verbal objection, defensive movement of head, hand or feet or prolonged cough, this could be considered as clinically significant discomfort

No definition was provided for "airway obstruction", "hypoxia" or "treatment-emergent cardiovascular adverse events", but the study author provided the details in the Results

Two consultant anaesthetists: One was responsible for performing the awake nasal fibreoptic intubation and scoring sedation, endoscopy, intubation and postintubation conditions, and the other administered the study drugs. A resident anaesthetist collected anaesthetic data and postoperative records. The intubating anaesthetist and the resident anaesthetist were all blinded to the study drugs used

Qiu 2013

Methods

Design: randomized, double-blinded study

Setting: a hospital affiliated with the Universtiy medical school

ParticipantsSixty participants with difficult airway and Mallampati score >= III were selected and randomly divided into four groups (D1, D2, D3 and MF, n = 15) by simple random method Nasal intubation with fibreoptic bronchoscopy was performed in all participants
InterventionsParticipants in groups D1, D2 and D3 intravenously received 0.5, 1.0 and 1.5 μg/kg dexmedetomidine 15 minutes before intubation, respectively. Participants in group MF were intravenously treated with 0.02 mg/kg midazolam and 2.0 μg/kg fentanyl five minutes before intubation
Outcomes

Discomfort during awake fibreoptic intubation (Participants were assessed on a scale of one to five: one: no movement; two: grimacing; three: mild cough; four: major limb movement; five: prolonged cough)

Intubation time (from insertion of fibreoptic scope to confirmation of nasal tracheal intubation)

Airway obstruction

Hypoxia

Treatment-emergent cardiovascular adverse events

Notes

We converted ordinal outcome measures to dichotomous outcome measures by identifying cut-off points on rating scales and dividing participants accordingly into 'clinical significant response' or 'no clinical significant response'. It was generally assumed that if participants displayed major limb movement or prolonged cough, this could be considered as clinically significant discomfort

One researcher was responsible for performing the awake nasal fibreoptic intubation and for scoring sedation, endoscopy, intubation and postintubation conditions, another administered the study drugs and the third collected anaesthetic data and postoperative records. All were blinded to the study drugs used

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