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CLINICAL INVESTIGATION
Year : 2009  |  Volume : 53  |  Issue : 4  |  Page : 442-449 Table of Contents     

Randomized Comparative Efficacy of Dexamethasone to Prevent Postextubation Upper Airway Complications in Children and Adults in ICU


1 Senior resident, Department of Anaesthesiology And Critical Care, Govt Medical College Jammu, Srinagar, India
2 Associate Professor, Department of Anaesthesiology And Critical Care, SKIMS, Srinagar, India
3 Professor, Department of Anaesthesiology And Critical Care, SKIMS, Srinagar, India
4 Ex.Professor and head, Department of Anaesthesiology And Critical Care, Govt Medical College Jammu, Srinagar, India

Date of Web Publication3-Mar-2010

Correspondence Address:
Dinesh Malhotra
Department of anaesthesiology and critical care, Govt.Medical College Jammu, J&K
India
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Source of Support: None, Conflict of Interest: None


PMID: 20640206

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Prophylactic steroid therapy to reduce the occurrence of postextubation laryngeal edema is controversial. Only a limited number of prospective trials involve adults and children in an intensive care unit. The purpose of this study was to ascertain whether administration of multiple doses of dexamethasoneto critically ill, intubated patients reduces or prevents the occurrence of postextubation laryngeal edema / stridor and its risk factors .Another specific objective of our study was to investigate whether an after-effect (that is, a transient lingering benefit) exists 24 hours after the discontinuation of dexamethasone In a prospective, randomized, double-blind control study, a total of 120 patients were randomly allocated both in children and adult population, who were ventilated more than 24 hours in ICU; into study and Control group. Study group comprising 60 patients with 30adults and 30 children. Study group adults received 8mg dexamethasone 4 doses i.e 4 hours prior to planned extubation, at extubation and 6 and 12 hours after extubation. Children received 0.5 mg.Kg -1 dose with maximum of 8mg at similar intervals. Control group comprising of 30 adults and 30 children who received placebo or saline at similar intervals. There was statistically significant difference (p = 0.019) in comparison of failed extubation (those who cannot withstand extubation and reintubated) in children with respect to adults. Moreover, duration of intubation (p =0.014) and female gender were also risk factors for failed extubation. We concluded that prophylactic use of intravenous dexamethasone is useful in preventing postextubation laryngeal edema/stridor in children but not in adults.

Keywords: Postextubation: Complications: Laryngeal edema: Strdor: Dexamethasone


How to cite this article:
Malhotra D, Gurcoo S, Qazi S, Gupta S. Randomized Comparative Efficacy of Dexamethasone to Prevent Postextubation Upper Airway Complications in Children and Adults in ICU. Indian J Anaesth 2009;53:442-9

How to cite this URL:
Malhotra D, Gurcoo S, Qazi S, Gupta S. Randomized Comparative Efficacy of Dexamethasone to Prevent Postextubation Upper Airway Complications in Children and Adults in ICU. Indian J Anaesth [serial online] 2009 [cited 2019 Nov 17];53:442-9. Available from: http://www.ijaweb.org/text.asp?2009/53/4/442/60315


   Introduction Top


End otracheal intub ation is a routine maneuver in Intensive Care Unit used to provide a patent airway and various modes of positive pressure ventilation in critically ill patients. [1] Laryngotracheal injury related to intubation may cause narrowing of the airway due to edema of the glottis. Laryngeal edema is more common after endotracheal intubation for more than 36 hours [1] . Edema inthis region is associated with the increased risks for postextubation stridor, which increase reintubation rate, aprocess referred to as failed extubation.

Reintubation may result in mothidity and mortal­ity [2],[3],[4],[5],[6] . Prolonged intubation or excessive endotracheal tube cuffpres sure can initiate mucosal erosion and car­tilage necrosis followed bytracheal stenosis. [2] Mortal­ity associated with reintubation has been estimated to be as high as 30% to 4Q% [4],[6] . Because the presence of an endotracheal tube (ELI) precludes direct visualiza­tion of the upper airway, recognition of the edema due to laiyngotracheal injury is often difficult be as high as 30% to 40%4,6 The prevalence of postextubation stridor ranges between 6% and 37% in intubated patients [7],[8],[9],[10],[11],[12]

Factors that may increase the likelihood of air­way damage include repeated passage of endotracheal tube, prolonged intubation for more than 24-hours and alarge size of endotrachealtube in relation to the size of the glottis, low Glasgow Coma Scale score, and fe­male sex. Female sex is at ahigher risk of developing complications probably because ofsmaller size of lar­ynx in comparison to males. [13],[14] Mucosalmembrane in males tends to be more resistant to trauma. [15] Cer­vical flexion and extension, inspiration, cough and deglutination can all affect the relative position of lar­ynxand endotrachealtube. Dynamic interactions may cause injury eitherby alternations in pressure on the mucosa orby frictional erosion [16]. Radiographic ex­amination has shown that endotrachealtub e can move 3.8 cm when head is moved from flexionto extension [17] .

Laryngeal edema is most commonly symptom­atic in children because of their small airway size, more severely reduced in cross-sectional area by edema. Reactive subglottic edema m children atthe cricoid ring can leadto post extubation stridor. [18] Laryngeal edema has been reported after tracheal extubation as one of the serious complications and causes significant mor­bidity as well as prolongs the stay in ICU. Pre-extuba­tion dexamethas one therapy could prevent the compli­cations of pro longed mtubation which becomes obvi­ous atthe time of extubation. By reducingthe degree of laryngeal edema, corticosternids may reduce the in­cidence ofreintubation orfailed extubation, which has clinical, economical and ethical problems in patients admitted in ICU. [9],[10]

Controversy still exists regarding the effectiveness ofprophylactic steroid therapy for patients at nskfor postextubation stridor [19],[20],[21],[22] . Some studies involving postextubation stridor and analyses of outcomes for those receiving steroids during intubation have yielded inconclusive ornegative results [19] . Only alimited num­ber of randomized trials involving adults and evaluating the benefits of cortico steroid therapy prior to extuba­tion have been conducted [21],[22] . Moreover, studies re­gardmgthe efficacy of prophylactic corticosteroids for intubated patients have yielded conflicting results due to differences in the number of doses, types of corti­costeroids, and timing and methods of administration to adult patients.

In our clinic al practice, the planned extubation was usually performed four hour afterthe first injection of multiple prophylactic doses of dexamethasone. Some­times, due to unpredictable conditions, critically ill pa­tients need to delay the planned extubation after ste­roid treatment. Previous studies reported that most high­risk patients susceptible to postextubation upper air­way edema who fail extubation require reintubation within 48 to 72 hours [3],[23] . However, little is known aboutthe after-effect of multiple-dose dexamethasone to prevent post extubation stridor.

The present study aims to determine the role of intravenous dexamethasone in preventing postextubation laryngealedemalstridorin adults and children who were undergo ingtheir first elective extubation in an ICU. The specific objectives of our study were to determine whethermultiple doses of dexamethasone are effective to reduce or prevent postextubation airway obstruc­tion and to investigate whether an after-effect (that is, a transient lingering benefit) exists 24 hours afterthe dis­continuation of dexamethasone.


   Methods Top


Atotal of 120 pediatric and adult patients who were admitted to the medical ICU between Jan 2003to Feb 2006 were included in the study as approved by our local ethical committee. This was prospective, ran­domized, double blind, placebo-controlled study. Af­ter obtaining informed consent from the patients ortheir relatives, stratified random sampling was employed to select adults and children in 1:1 ratio among patients fulfilling eligibility criteria. The patients were then ran­domized in each group separately to receive either Dexamethas one or Placebo. The procedure adopted was permuted block randomization in orderto keep equal numbers in each group.

The patients who were on ventilators (Puritan bennett840) for more than 24 hours were studied in ICU. All intubations were performed by a qualified experienced Anaesthetist in the operating room or in Accidental Emergency. Trachea was intubated with the standard endotracheal tube size according to their age. Children less than 10 yrs were intubated with uncuffed endotracheal tube. All patients requiring prolonged in­tubation and mechanical ventilation were sedated or paralyzed accordingto individual need to prevent agi­tation and excessive movement of the endotracheal tube, orinterference with the ventilator. Routine nurs­ing care included ETTsuctioning every two hours and as needed to maintain a patent airway. The admitting diag­nosis ranged from postoperative recoveryto trauma.

Exclusion Criteria: -

Followingpatients were not included in our study.

  1. Patients having upper airway disease.
  2. Patients who had undergone neck surgery.
  3. Any anatomicaldeformity ofupper airways
  4. Patients already on steroids.


In our study, patients were randomly assigned to two groups:-Study group and Control group.

1. Study Group comprising 60 patients with 30 adults and 30 children. In adults dexamethasone 8mg bolus i.v was given 4 hours priorto planned extuba­tion, at extubation and at 6 and 12 hours after extuba­tion.

In children, dexamethasone 0.5 mg kg -1 i.v with maximum of 8mg was given atsimilar intervals.

2. Control Group:-comprising 30 adults and 30 children who received placebo or saline at similar in­tervals.

The dexamethasone and the placebo were pre­pared in identical volume and labeled as A and B in a syringe to ensure administration in double blind fash­ion; neither the intensivist orderingthe drugs northe person administering them was aware of the drugs be­ing given to the patient till the end of the study.

Endotracheal extubations were followed accord­ungto standard ICUweanulg protocol (ventilators used were Puritan Bennett 840 touch screen) as under: -

  1. Temperature of less than or equal to 38°C for more than eight hours,
  2. Discontinuous use of sedatives,
  3. Heart rate of more than or equal to 70 beats per minute and less than orequalto 130 beats per minute,
  4. Systolic blood pressure (SBP) of more than or equal to 80 mm Hg in the absence ofvasopressor,
  5. Fraction of inspired oxygen (Fi0 2 )of less than or equal to 60%, partial pressure of oxygen (PaO,) of more than or equalto 60 mm Hg, and Pa0 2 1FiO 2 mtio of more than 200,
  6. Positive end-expiratory pressure (PEEP) ofless than or equal to 5 cm H 2 O,
  7. Respiratory rate = < 40/min
  8. Minute ventilation of less than or equal to 15 liters perminute, and
  9. pH ofmore than orequalto 7.3.
  10. StaticCompliance (CST)> 33ml/cmH2O


Supplemental oxygen was continued to maintain an oxygen saturation of more than 95% as measured by a pulse oximeter.

All patients were clinically assessed for stridor, laryngeal edema (postextubation obstruction) after extubation forup to 24 hrs. The person assessing the parameters was unaware of the drug the patient had received. The patients with respiratory dis­tress were assigned to take non-invasive positive­pressure ventilation (bi-level positive airway pres­sure Puritan Bennett USA) by face mask ifthey failed in response to two doses ofepinephrine inhalation and exhibited at least two of the following criteria of respiratory distress:

  1. Respiratory acidosis (defined as an arterialpH of less than 7.35 with apartialpressure of arterial carbon dioxide of more than 45 mm Hg),
  2. Clinical signs suggestive ofrespiratoty-muscle fa­tigue orincreased respi atory effort (thatis, use of ac­cessory muscles, intercostal retraction, or paradoxical motion of the abdomen),
  3. Arespiratoty rate of more than 25 breaths per minute fortwo consecutive hours, and
  4. Hypoxemia (defined as an arterialoxygen saturation of less than 90%ora PaO2of less than 80mmHg with a FiO2ofmore than 50%.


Patients were reintubated with mechanical venti­lation support ifthey met at least one of the following criteria:

  1. A pH of less than 7.3 with a partial pressure of carbon dioxide increase of more than 15mm Hg,
  2. A change in mental status rendering the patient un­able to tolerate non-invasive ventilation,
  3. A decrease in the oxygen saturation to less than 85% despite the use ofa high Fi0 2 (a PaO 2 of less than 50 mm Hg with an Fi0 2 ofmore than 70%),
  4. Lackof improvement in signs of respiratory-muscle fatigue,
  5. Hypotension with an SBP of less than 80 mm Hg form ore than 30 minutes despite adequate volume chal­lenge,
  6. A diastolic blood pressure drop of more than 20 mm Hg, or
  7. Copious secretions that could not be cleared adequately or thatwere associatedwith acidosis, hypoxemia, or changes inmental status (somnolence, agitation, or diaphoresis).


Assessment of Airway status in adults and chil­dren was done as (Deming and Oech [19] ):­

  1. Laryngeal Dyspnea *Present/Absent
  2. Laryngeal Stridor * * Present/Absent
  3. LaryngealEdema - Present/Absent


Evidenced during Laryngoscopy (Laryngo scopy is the gold standard method for diagnosing Postextubation Laryngeal Edema [24]

* Laryngeal Dyspneadefmed as occurrence of signs of upper airway obstruction i.e., prolonged In­spiratory phase associated with recruitment of acces­sory respiratory muscles.

Laryngeal stridor defined as crowing sound present with inspiration.

Scoring for stridor in children was done as:­ 0. No stridor

  1. Stridorwhile crying
  2. Stridor at rest
  3. SevereBiphasic chest retractions


Statistical analysis

Baseline characteristics were compared in both groups; ascertain comparability by using appropriate statistical tests. Chi-squaretest (x 2) and Fisher's exact`t' test were used to evaluate difference in categorical data while unpaired `t' test was used to evaluate statistical significance in mean values.

All analysis was performed by using computer software SPSS ver. 10.0forwindows and p-value of X0.05 was considered of statistical significance.


   Results Top


Following observations were made in our study:­

1. There was no statistically significant difference (p>0.05) among the groups in respect of age, sex, ad­mittingdiagnosis, ICU stay, intubation type and dura­tion ofintubation.[Table 1] and [Table 2] and [Table 3] and [Table 4]

2. There was statistically significantdifference (p =0.019) in comparison offailed extubation in children with respect to adults. In Dexamethasone group, in chil­dren 30% cases were of failed extubation while in con­trol group, it was 63.33%. [Table 5].

3. On comparison between duration of inubation with incidence of failed extubation in adults in Dexa group, we found that with duration of inubation >72 hours, failed extubation incidence was high with statis­tical significanee (p=0.014). Similarly in Control group, incidence offailed extubation with respectto duration of inubation was statistically significant (p = 0.028). In children, in Dexamethasone group, the incidence of failed extubation with duration of enubation less than 72 hours was 22.22% while duration of intubation more than 72 hours was 41.67%. This difference although more with longer duration of intubation (more than 72 hours)butwas statistically insignificant. [Table 6]

4. There was statistically significant variation on comparison of failed extubation/laryngeal edema inci­dence with that of sex. In Dexamethasone group, in adults 72.73%females had laryngeal edemawhich was statistically significant (p = 0.035). While in Control group, 70.59% females had failed extubation/ laryn­geal edema. Although females had significant high inci­dence of failed extubation/laryngeal edema in Control group but did not reach statistical significance. [Table 7].

5. Only in children betweentwo groups,there was highly statistical significance m Airway assessment sta­tus (p = 0.004). Laryngeal edema was more in Control group (63.33%) in children as compared to Dexam­ethasone group (26.67%). While in adult patients there was an equivocal response in incidence of failed extu­bation/laryngeal edema between two groups. [Table 8]


   Discussion Top


The potential benefit of steroids to laryngeal edema is presumably based on its anti-inflammatory actions, which inhibitthe release of inflammatory mediators and decrease capillary permeability. The risk ofhann from steroid therapy for 24 hours or less to prevent postextubation laryngeal edema is negligible [21],[22],[23] The extent of the effect of prophylactic steroids on airway obstruction is still a matter of some controversy.

We conducted this randomized clinical trial to evaluate the effects of prophylactic dexamethasone therapy in preventing latyngealedema for adult patients and children in ICU setting. The choice of dexametha­sone was based on its high anti-inflammatory potency, negligible mineral corticoid effects attherapeutic doses, and long duration of action [24] . We investigated the af­ter-effect until 24 hours after the last dose of dexam­ethasone.

The incidence of laryngeal edema/stridorin our study, after extubation patient population has been re­ported to range from 26.67-36.67% which are not comparable to reports in literature ranging from 3-22%. [1],[10] This higher incidence oflatyngeal edema and stridor is found to be associated with by many authors [2],[3],[7] These results in literature, however, were obtained in studies evaluating shorttemi operative intubations; these studies did not include patients with wide spectrum of diagnosis & prolonged period ofintubation as is prac­ticed in our study.

The increased incidence of laryngeal edema may be due to the fact that our study intended to select pa­tients who required longer duration ofintubation more than 24houi and because of logistic concerns (4 doses of dexamethasone).

Our findings of steroid effect in reducing postextubation stridor were consistent with the results of the two recent studies in adult medical and surgical ICU settings [2l],[22] . In a recent study with a large number of subjects, Francois and colleagues [22] reported that fourdoses of 20 mg ofmethylprednisolone, given at fourhour intervals, significantly reducedthe incidence ofpostextubation stridorfrnm 22% to 3% and reduced the incidence of reintubation from 8% to 4%. How­ever, the subjects in this study were not restricted to the high-risk patients for postextubation laryngeal edema (unlike the subjects in our study). The reduction of postextubation stridorin ourstudy was statistically sig­nificant, but not as dramatic as that of the study of Cheng and colleagues [21] . Anotherreason forthis discrepancy may be the difference in the timing ofextubation. Cheng and colleagues executed the extubation one hour after methylprednisolone administration over the span of 24 hours. The after-effectof dexamethasone validates the reduced incidence of postextubation stridor after mul­tiple doses of dexamethas one.

The development of stridor is unpredictable and this type of acute upper airway obstruction can be char­acterized by range of symptoms ranging from hoarse­nessto severe obstruction requiring reintubation. More­over, female sex is also risk factor for laryngeal edema identified in our study. Several authors have also stressed female gender as risk factor. [11],[12],[13]. Our study results are in agreement with studies [1],[10],[14],[15],[16] who con­cluded that postextubation stridor was reduced in chil­dren with prophylactic administration of dexametha­sone, but in adults, it didnot appearto reduce the need for reintubation.

Our results are contradictory to the studies done by Gauss orgues P [11] , Courtney [17] , Tellez D [l8] who dem­onstrated that incidence of laryngeal edema/stridor was not modified by corticosternids (Dexamethasone).

Our study have substantiated that corticosteroids confer the benefits in children at high risk for postextubation laryngeal edema, whereas arnutine pro­phylactic use of corticosteroids to prevent postextubation stridorin every intubated patient is un­warranted. Dexamethasone and other steroids, in ap­propriate doses, can be helpful in alleviating laryngeal edema in intubated high-riskpatients susceptible to air­way obstruction, such as those requiring repeated or prolonged intubations.

Based on this information, clinicians should con­sider initiating prophylactic corticostemid therapy in this population. However; further studies are needed to es­tab lish the optimal dosing regimens as well as the sub­groups of patients at high risk forp ostextubation laryn­geal edema who will derivethe greatest benefit from this preventive steroid therapy.



 
   References Top

1.Dannon JY, Rauss A, Dreyfuss D, et al. Evaluation of risk factors for laryngeal edema after tracheal extubation in adults and its prevention by dexamethasone. A placebo controlled, double blind, multi center study. Anesthesiology 1992; 77:245-51.  Back to cited text no. 1      
2.Arensman et al. Intravenous dexamethasone for extu­bation of newborn infants. Cochrane library 1988.  Back to cited text no. 2      
3.Esteban A,Alia I, Tobin MJ, Gil A, Gordo F, Vallverdu I, BlanchL, Bonet A, Vazquez A, de Pablo R, et al. Effect of spontaneous breathing trial duration on outcome of at­ tempts to discontinue mechanical ventilation. Am J Respir Crit Care Med 1999;159:512-518.  Back to cited text no. 3      
4.Jaber S, Chanques G, Matecki S, Ram onatxo IA, Vergne C, Souche B, Perrigualt PF, Eledjam JJ. Postextubation stridor in intensive care unit patients. Risk factors evaluation and importance of the cuff-leak test. Intensive Care Med 2003,29:69-74.  Back to cited text no. 4      
5.Epstein SK, Ciubotaru RL, gong JIB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997,112:186-192.  Back to cited text no. 5      
6.ConradyPA, GoodmanLR, et al . Alteration of endotra­cheal tube positions. Crit Care Med 1976; 4: 8-12.  Back to cited text no. 6      
7.Kalloghlian AK, BM Pittappilly and NT Mathews, et al. Effect of dexamethasone on incidence of post extu­bation stridorin pediatric patients. Crit Care 1999; 3:12­16.  Back to cited text no. 7      
8.Meade MO, Guyatt GH, CookDJ, et al. Trials of co rti­costeroids to prevent post extubation airway complica­tions. Chest 2001;120 (6 suppl); 464-85.  Back to cited text no. 8      
9.Markovitz BP, Randolph AG Corticosteroids for pre­vention and treatment of post extubation stridor in neo­nates, children and adults. Paed Crit Care Med 2002; 223-226.  Back to cited text no. 9      
10.Anene O, Meert KL, UY H, et al. Dexamethasone for prevention of post extubation airway obstruction; a prospective, randomized, double blind, placebo, con­trolledtrial. Crit Care Med 1996; 24: 1666-9.  Back to cited text no. 10      
11.Bishop Ivll, Weymuller EA, Fink BR. Laryngeal effects of prolonged intubation. AnesthAnalg 1984; 63:335-342.  Back to cited text no. 11      
12.Gaussorgues P, Boyer F, pipemo D, et al. Role of corti­costeroids in prevention of post extubation laryngeal edema. Press Med 1987;16: 1531-2.  Back to cited text no. 12      
13.Gaynor EV Greenberg SB. Untoward sequelae of pro­longed intubation. Laryngoscope 1985; 94: 367 -377.  Back to cited text no. 13      
14.Harrison GA, Tonkin JP. Prolonged endotracheal intu­bation. BJA 1968 ; 40: 241-9.  Back to cited text no. 14      
15.MC GovernFH, Fitz- Hug GS, EdgemonLJ. The hazards of endotracheal intubation. Ann Otol Rhinol Laryngol 1971:80:556-64.  Back to cited text no. 15      
16.KoKa B V Jeon ID, Andre SM. Post intubation croup in children. AnesthAnalg 1977;56: 501-5.  Back to cited text no. 16      
17.Freezer N, Butt W, Phelan P. Steroids in croup: do they increase the incidence of successful extubation? Anaesthlntensive Care 1990;18: 224-8.  Back to cited text no. 17      
18.Courtney and Couser, et al. Intravenous dexamethasone for extubation of newborn infants. Cochrane Review 1992  Back to cited text no. 18      
19.Tellez D\\ Gavis AG, et al Dexamethasone in the pre­vention of post extubation stridor in children. J Pediat­ric 1991;118: 289-94.  Back to cited text no. 19      
20.Deming MV Oech SR. Steroid and antihistamine therapy for post extubation subglottic edema. Anesthesiol­ogyl 961 22 933-936.  Back to cited text no. 20      
21.Cheng KC, Hou CC, Huang HC, Lin SC, Zhang H. Intra­venous injection of methylprednisolone reduces the incidence ofpostextubation stridor in intensive care unit patients. Crit CareMed 2006; 34:1345-1350.  Back to cited text no. 21      
22.Francois B, BellisantE, Gissot V, Desachy S, Boulain T, Preux P-M, Vignon P. 12-h pretreatment with methyl­prednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomized double­blindtrial.Lancet 2007; 369:1083-1089.  Back to cited text no. 22      
23.Bladimir G, Fernando FV, Andres E. Deleterious effects of reintubation ofmechanicallyventilated patients. Clin Pulmon Med2003, 10:226-230.  Back to cited text no. 23      
24.Russel J Roberts, Shannon M, et al. Cortico steroids for prevention of postextubation laryngeal edema in adults. The Annals of Phann acotherapy 200 8;5 : 686-691.  Back to cited text no. 24      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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