|Year : 2017 | Volume
| Issue : 4 | Page : 828-833
Comparison of dexmedetomidine and midazolam for sedation in mechanically ventilated patients guided by bispectral index and sedation-agitation scale
Manoj Tripathi1, Virendra Kumar1, Mahendra B Kalashetty2, Deepak Malviya1, Prateek Singh Bais1, Om Prakash Sanjeev1
1 Department of Anesthesia and Critical Care, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Shri B.M. Patil Medical College, Bijapur, Karnataka, India
|Date of Web Publication||28-Nov-2017|
Department of Anesthesia and Critical Care, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow - 226 010, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Mechanical ventilation and sedation are inextricably linked components of critical care that represent, what we do for the patients during their vulnerable course in Intensive Care Unit (ICU). Aims: The aim of this study is to compare the efficacy and safety of midazolam and dexmedetomidine in patients on mechanical ventilator with the help of Bispectral Index (BIS) monitoring and correlation of BIS with Sedation-Agitation Scale (SAS). Settings and Design: Prospective, observational, and comparative study. Materials and Methods: In this study, recruited patients were allocated into two groups of 14 patients each. Group A and Group B patients received injection dexmedetomidine and injection Midazolam, respectively. Hemodynamic parameters, time of extubation, duration of mechanical ventilation, and mortality were compared between two groups. Statistical Analysis: Mean and the standard deviation were calculated. Test of analysis between two groups was performed using unpaired t-test. We applied correlation technique, that is, Pearson product-moment correlation coefficient (r) to assess the correlation between BIS and SAS. It varies from + 1–0 to −1. Results: Heart rate and blood pressure were more stable and less in Group A than Group B. Duration of mechanical ventilation was found extremely significant between Group A (77.86 ± 5.71 h) and Group B (95.64 ± 17.00 h) (P = 0.001). There was significant difference found in the time of extubation between Group A (21 ± 6.44 h) and Group B (30.4 ± 10.62 h) P = 0.008. Conclusion: It is concluded in this study that sedation with dexmedetomidine resulted in quick extubation and decreased the duration of mechanical ventilation in comparison to midazolam in ICU patients. There was found moderate to high correlation between BIS index and SAS.
Keywords: Bispectral Index, dexmedetomidine, Intensive Care Unit sedation, midazolam, Sedation-Agitation Scale
|How to cite this article:|
Tripathi M, Kumar V, Kalashetty MB, Malviya D, Bais PS, Sanjeev OP. Comparison of dexmedetomidine and midazolam for sedation in mechanically ventilated patients guided by bispectral index and sedation-agitation scale. Anesth Essays Res 2017;11:828-33
|How to cite this URL:|
Tripathi M, Kumar V, Kalashetty MB, Malviya D, Bais PS, Sanjeev OP. Comparison of dexmedetomidine and midazolam for sedation in mechanically ventilated patients guided by bispectral index and sedation-agitation scale. Anesth Essays Res [serial online] 2017 [cited 2017 Dec 13];11:828-33. Available from: http://www.aeronline.org/text.asp?2017/11/4/828/207078
| Introduction|| |
Patients admitted to the Intensive Care Unit (ICU) are usually in need of invasive and uncomfortable interventions such as mechanical ventilation. To reduce anxiety, increase tolerance, and improve outcomes of such interventions, sedation is common practice. Conventionally, sedative agents administered in the ICU are g-aminobutyric receptor agonists which include the benzodiazepines (usually midazolam) and propofol. Optimum sedation is vital in striking a balance between providing pain relief and maintaining patient calm while preventing over-sedation and unnecessarily lengthy ICU stays. Many protocols advise daily sedation interruptions to assess the level of sedative in the patient and to avoid over-sedation. Due to limitation of subjective sedation scales to assess ICU sedation, over-sedation and under sedation are the major challenges in the ICU management. To overcome this, Bispectral Index (BIS), an objective tool to assess sedation and consciousness is now being used in critical care setting.
Dexmedetomidine, a highly selective α2 agonist, has sedative, analgesic, and sympatholytic properties. Activation of the receptors in the brain and spinal cord inhibits neuronal firing, causing sedation, analgesia, hypotension, and bradycardia. In addition to reduced respiratory depression, dexmedetomidine scores over the currently used ICU sedatives such as midazolam and propofol in having analgesic properties that help reduce the opioid requirement and the associated side effects.
In this study, we compare the efficacy and safety of the two sedative drugs that are midazolam and dexmedetomidine in patients on mechanical ventilator with the help of BIS monitoring and correlation of BIS with Sedation-Agitation Scale (SAS). We also observe the effect of sedation on morbidity and mortality of the patient.
| Materials and Methods|| |
This study was conducted on 28 patients of either sex ranging from 20 to 60 years, requiring mechanical ventilation in ICU at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow. Patients admitted to ICU requiring mechanical ventilatory support were eligible for enrolment. Exclusion criteria include transfer from outside institution, admission after resuscitation from cardiac arrest, head injury patients, impaired hearing, impaired visual acuity such as blindness, facial and eye trauma, severe hepatic derangement, renal insufficiency requiring dialysis, and patient on neuromuscular blockade.
The patients were divided into two groups of 14 patients each:
- Group A: Patients received injection dexmedetomidine
- Group B: Patients received injecion midazolam.
Written consent was obtained from every patient's relative. All the patients were examined thoroughly and relevant routine investigations such as hemoglobin, total and differential leukocyte counts, platelet count, serum creatinine, serum urea, blood urea nitrogen, serum bilirubin, serum electrolytes including sodium, potassium, and calcium were done. Arterial blood gas was done in all patients. Special investigations if required were performed accordingly. Choice of sedation and/or analgesic regimens was made at the discretion of team of intensivists, independent of the BIS score.
Injection dexmedetomidine infusion was started with a loading dose of 1 μg/kg over 10 min followed by the infusion at the rate of 0.2–0.7 μg/kg/h. Dosage was adjusted to maintain a BIS score of 60–80 or a SAS of 3 or 4 during mechanical ventilation. Injection midazolam is given as an initial intravenous bolus of 0.5–5 mg every 1–5 min as needed. Continuous infusion at 1–2 mg/h, doses to be increased in increments of 1–2 mg/h until adequate sedation is achieved as with dexmedetomidine.
After wiping the patient's forehead and temple with alcohol and drying the skin to ensure that a quality signal will be obtained, sensor placed across the patient's forehead and over the left or right temple. The BIS index displayed on the monitor as a number recorded. Continuous intravenous sedatives infusion (midazolam or dexmedetomidine) were given for the first 8 h to every patient, who had SAS score ≥4; then sedatives were adjusted and on as and when required basis to achieve a score of 3 or 4 on SAS scale. Injection tramadol (intramuscular) was given to ensure adequate analgesia, it was administered to all patients according to the need, based on nurses assessment of the level of analgesia, which is as follows: (1) Denotes extreme pain, (2) severe pain, (3) moderate pain, (4) slight pain, (5) no pain. Injection tramadol was administered in response to a score of 1–4 and was continued until the pain was considered to be adequately controlled. Simultaneous recording of the clinical sedation scale (Riker's SAS), sedative drugs, and BIS index done at every 4 h for the first 24 h, then every 8 hourly. Sedation assessment was performed before recording the BIS value to avoid bias. Time to extubation after the sedative drug had been stopped was noted and total duration of mechanical ventilation was also noted. Data were collected until patients were extubated. Hemodynamic parameters such as pulse rate (PR), blood pressure, SpO2, electrocardiogram, and temperature were also monitored. A thorough assessment of patient's condition such as chest, cardiovascular system, urine output, mental status, and PaO2/FiO2 ratio to see lung injury was done on daily basis.
SAS  was applied to see clinical sedation score which is as follows:
- 7 - Dangerous agitation
- 6 - Very agitated
- 5 - Agitated
- 4 - Calm and co-operative
- 3 - Sedated
- 2 - Very sedated
- 1 - Unarousable.
Data obtained from the patients under study were recorded in a standard performa. The parametric data were expressed as mean ± standard deviation. Comparison between two groups was performed using t-test. The value of P < 0.05 was considered statistically significant and a P > 0.05 was not considered statistically significant. On the basis of observations, relationship between BIS and SAS measured by “correlation coefficient.” We applied correlation technique that is Pearson product-moment correlation coefficient (r). It varies from + 1–0 to − 1.
- r ≥ 8: High correlation coefficient
- r = 0.4–0.7: Moderate correlation coefficient
- r ≤ 0.3: Low correlation coefficient
- r = 0: Absolutely no correlation.
| Observations and Results|| |
In Group A, the male:female ratio was found to be 1:1 and in Group B it is 1:1.3. The distribution was almost symmetrical in both the groups. Age-wise distribution of patients in both the groups was also found to be symmetrical. The majority of patients belong to age group 20–30 years.
[Graph 1] shows the variation of PR before and after sedation at a different time interval in Group A and Group B patients. Mean of the PRs of all patients in Group A before sedation was 120 beats/min (bpm). The reduction in mean PR after 15 min of sedation was 7.4% and after 1 h the reduction was 13%. The maximum reduction of PR in this group was 25.5% after 24 h of sedation. Mean of the PR in Group B before sedation was found to be 124 bpm. While in this group, reduction in mean PR was 3.2% after 15 min and 2.7% after 1 h of sedation, the maximum reduction was observed after 24 h that was 6.9%. [Graph 2] showing the variation in mean arterial blood pressure (MAP) with sedation in Group A and Group B, respectively. Mean of MAP of all the patients in Group A before sedation was 102.43 mmHg. The reduction in MAP was 6.4% after 15 min of sedation 11.5% after 1 h of sedation. The maximum reduction in MAP was after 48 h that was 20%. The mean of MAP in Group B patients before sedation was 88.85 mmHg. The reduction in MAP was 1.2% after 15 min of sedation 2.4% after 1 h of sedation. The maximum reduction in MAP was after 4 h that was 5.2%. As shown in [Table 1], duration of mechanical ventilation was found extremely significant between Group A (77.86 ± 5.71 h) and Group B (95.64 ± 17.00 h) (P = 0.001). Total sedative drug consumption in Group A was 1617 μg and in Group B was 70.71 mg. In Group A before sedation, the BIS varied between 88 and 98 and SAS varied between 5 and 6. We found that there was a moderate correlation (r = 0.616) before sedation. While after sedation, there was high correlation (r = 0.85 after 15 min, r = 0.821 after 1 h, r = 0.831 after 4 h, r = 0.87 after 8 h). There was low correlation after 3rd day when most of the patients in this group were being weaned from mechanical ventilation.
|Table 1: Duration of mechanical ventilation and total drug consumption in Group A and Group B|
Click here to view
Similar to those in Group A patients, in Group B patients, there was a moderate correlation (r = 0.631) before sedation. While after sedation there was high correlation (r = 0.84 after 15 min, r = 0.89 after 1 h, r = 0.85 after 4 h, r = 0.83 after 24 h). There was low correlation after the 3rd day when most of the patients in this group were being weaned from mechanical ventilation. The findings were similar to that of Group A. [Table 2] shows time of extubation after sedation drug is discontinued in both the groups. There was significant difference found between Group A (21 ± 6.44 h) and Group B (30.4 ± 10.62 h) P = 0.008. As shown in [Graph 3], hypotension, bradycardia, and cardiac arrhythmia was found in Group A patients while delayed awakening was more prevalent in Group B. In the present study, three patients expired in Group A and four patients expired in Group B. Although mortality was higher in Group B, on statically evaluation the difference was not significant (P < 0.05).
|Table 2: Time of extubation after sedation drug is discontinued in Group A and Group B patients|
Click here to view
| Discussion|| |
In the present study, we tried to compare the efficiency of dexmedetomidine and midazolam in ICU sedation. Besides that, the study shows a correlation between BIS and SAS score with sedation and without sedation in both the groups.
The mean PR in both the groups was almost equal, that was 120 bpm for Group A and 124 bpm for Group B before sedation. After sedation, in Group A, heart rate reduced more than Group B. We observed bradycardia in two patients in Group A. Except for interruption of infusion, no treatment is required. No incidence of bradycardia was noticed in Group B. One patient developed atrial fibrillation in Group A. Riker et al. found dexmedetomidine-treated patients were more likely to develop bradycardia. MacLaren et al. In his study, on the use of adjunctive dexmedetomidine therapy in intensive care patients found that bradycardia and hypotension were more common with the use of dexmedetomidine and out of forty patients 22 patients were extubated within 24 h of starting dexmedetomidine infusion which was earlier than other agents alone. These findings support the results of our study.
Mean arterial pressure was decreased more in Group A patients than Group B patients after the start of sedation. Two patients in the Group A had an incidence of hypotension that required drug interruption. While three patients who required ionotropic support expired during the treatment. There was no incidence of hypotension in Group B that required interruption of the drug. Four patients who required ionotropic support expired during the treatment in Group B. Martin et al. concluded the same findings that hypotension and bradycardia occurred more frequently in the dexmedetomidine group and pre-operative cardiovascular conditions were not risk factors for dexmedetomidine patients.
Dasta et al. had done a study on a total of 366 intubated ICU patients anticipated to require sedation for >24 h and concluded in his study that dexmedetomidine based sedation for ICU patients was significantly less costly than continuous infusion of midazolam. The reduction in total ICU cost was explained primarily by decreased cost of mechanical ventilation and ICU stay. Riker et al. compared dexmedetomidine and midazolam in mechanically ventilated patients in his study and concluded that At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension. The most notable adverse effect of dexmedetomidine was bradycardia. The median time of extubation was 1.9 days shorter and ICU length of stay was 1.7 days shorter in dexmedetomidine group. Siobal et al. in 2006, had published a pilot study using dexmedetomidine to facilitate extubation in ICU patients. They concluded that dexmedetomidine appears to maintain adequate sedation without hemodynamic instability or respiratory drive depression, and thus may facilitate extubation in agitated difficult-to-wean patients. A total of 24 trials involving 2419 critically ill patients from over 11 countries were identified and subjected to meta-analysis by Tan and Ho. This meta-analysis showed that significant heterogeneity existed between studies on dexmedetomidine. They concluded that dexmedetomidine reduced the length of ICU stay. The risk of bradycardia was, however, higher when both a loading dose and high maintenance doses of dexmedetomidine were used.
In the present study, duration of mechanical ventilation in Group A was shorter by 17.79 h as compared to Group B. Mean duration of mechanical ventilation in Group A patients was 77.86 ± 5.71 h. In this group seven patients were weaned successfully in <72 h, o which three patients required mechanical ventilation for <48 h. In contrast in Group B, mean duration of mechanical ventilation was 95.64 ± 17.00 h and only two patients were weaned in <72 h. No patient was weaned in <48 h in Group B. There was a significant reduction (P = 0.001) in the mean duration of mechanical ventilation in Group A as compared to Group B patients. The mean time to extubation in Group A was 21 ± 6.44 h and in Group B was 30.40 ± 10.62. We also found that in Group A one patient was extubated in as early as 8 h after the sedation was stopped, whereas in Group B, the minimum time to extubation was 18 h. Reade et al. studied dexmedetomidine versus haloperidol in delirious, agitated, and intubated patients. They concluded that dexmedetomidine significantly shortened median time to extubation from 42.5 h to 19.9 h (P = 0.016). Dexmedetomidine also decreased length of stay from 6.5 days to 1.5 days (P = 0.004) after drug commencement. This study also supports the results of our study. Thus, the results were similar to the above studies. The difference between the two groups in our study is less compared to the previous studies, probably because of the shorter duration of sedation in our study. In some previous studies, it is documented that dexmedetomidine is an alternative to traditional sedatives and analgesics in critically ill patients. The safety and efficacy of dexmedetomidine in adults likely persist beyond 24 h, without the emergence of rebound effects after discontinuation.
Ma et al. compared the reliability of BIS with SAS in assessing the depth of sedation in mechanically ventilated ICU patients. They concluded that SAS is well correlated with BIS in assessing the depth of sedation. BIS is an objective efficient tool for monitoring the depth of sedation in mechanically ventilated ICU patients, and it is more reliable than SAS especially when sedation levels reached to SAS 2–4. In the present study, we also observed that with increasing depth of sedation, there was an increase in correlation between SAS and BIS and was independent of drug used for sedation. Turkmen et al. showed that the significant correlation between Richmond Agitation-Sedation Scale and BIS values were found (r = 0.900, P = 0.0001). Most of the previous studies had supported the results of the present study except some. Frenzel et al. concluded that BIS values are correlated with only some ICU patients with the clinical assessment of sedation level.
Side effects are more common in Group A patients than Group B patients. In previous studies, it was documented that dexmedetomidine causes hypotension, bradycardia, and arrhythmia. In the present study, hypotension, bradycardia, hypertension, and atrial fibrillation were found in Group A patients while delayed awakening was found in Group B patients. In contrast, mortality was more common in Group B patients (29%) than Group A patients (21%). Although it was not statically significant (P < 0.05).
Pandharipande et al. compared dexmedetomidine and lorazepam in mechanically ventilated ICU patients. They concluded that sedation with dexmedetomidine resulted in more days alive without delirium and coma. The 28 days mortality in the dexmedetomidine group was 17% versus 27% in the lorazepam group (P = 0.18). These findings support the results of our study.
| Conclusion|| |
Both dexmedetomidine and midazolam were found to be efficacious and could achieve adequate sedation in patients requiring mechanical ventilation. Sedation with dexmedetomidine resulted in quick extubation and decreased the duration of mechanical ventilation in comparison to midazolam in ICU patients. There was moderate to high correlation between BIS index and SAS. Correlation increased as the sedation increased and was independent of the drug used for sedation. Dexmedetomidine has a higher incidence of bradycardia and hypotension.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mehta S, McCullagh I, Burry L. Current sedation practices: Lessons learned from international surveys. Anesthesiol Clin 2011;29:607-24.
Aitken LM, Bucknall T, Kent B, Mitchell M, Burmeister E, Keogh SJ. Protocol directed sedation versus non-protocol directed sedation to reduce duration of mechanical ventilation in mechanically ventilated intensive care patients. Cochrane Database Syst Rev 2012;4:CD009771.
Hynes-Gay P, Leo M, Molino-Carmona S, Tessler J, Wong C, Burry L, et al.
Optimizing sedation and analgesia in mechanically ventilated patients – An evidence-based approach. Dynamics 2003;14:10-3.
Regan K, Boyd O. Sedation practice: Is it time to wake up and embrace change? Crit Care 2008;12:102.
Gurudatt C. Sedation in Intensive Care Unit patients: Assessment and awareness. Indian J Anaesth 2011;55:553-5.
] [Full text]
Myatra S. Dexmedetomidine: Toward a paradigm shift in ICU sedation. Indian J Crit Care Med 2014;18:271-2.
] [Full text]
Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999;27:1325-9.
Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al.
Dexmedetomidine vs. midazolam for sedation of critically ill patients: A randomized trial. JAMA 2009;301:489-99.
MacLaren R, Forrest LK, Kiser TH. Adjunctive dexmedetomidine therapy in the Intensive Care Unit: A retrospective assessment of impact on sedative and analgesic requirements, levels of sedation and analgesia, and ventilatory and hemodynamic parameters. Pharmacotherapy 2007;27:351-9.
Martin E, Ramsay G, Mantz J, Sum-Ping ST. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the Intensive Care Unit. J Intensive Care Med 2003;18:29-41.
Dasta JF, Kane-Gill SL, Pencina M, Shehabi Y, Bokesch PM, Wisemandle W, et al.
A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the Intensive Care Unit. Crit Care Med 2010;38:497-503.
Siobal MS, Kallet RH, Kivett VA, Tang JF. Use of dexmedetomidine to facilitate extubation in surgical intensive-care-unit patients who failed previous weaning attempts following prolonged mechanical ventilation: A pilot study. Respir Care 2006;51:492-6.
Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: A meta-analysis. Intensive Care Med 2010;36:926-39.
Yu SB. Dexmedetomidine sedation in ICU. Korean J Anesthesiol 2012;62:405-11.
Reade MC, O'Sullivan K, Bates S, Goldsmith D, Ainslie WR, Bellomo R. Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: A randomised open-label trial. Crit Care 2009;13:R75.
Ma PL, Zhao JZ, Su JW, Li Q, Wang Y. Comparison of reliability of bispectral index and sedation-agitation scale in assessing the depth of sedation in patients treated with mechanical ventilation. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2006;18:323-6.
Turkmen A, Altan A, Turgut N, Vatansever S, Gokkaya S. The correlation between the Richmond agitation-sedation scale and bispectral index during dexmedetomidine sedation. Eur J Anaesthesiol 2006;23:300-4.
Frenzel D, Greim CA, Sommer C, Bauerle K, Roewer N. Is the bispectral index appropriate for monitoring the sedation level of mechanically ventilated surgical ICU patients? Intensive Care Med 2002;28:178-83.
Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, et al.
Effect of sedation with dexmedetomidine vs. lorazepam on acute brain dysfunction in mechanically ventilated patients: The MENDS randomized controlled trial. JAMA 2007;298:2644-53.
[Table 1], [Table 2]