Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care

Abstract

) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care. ]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period. -mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved. ]) after extubation in the ICU. Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation. ] of 3 or greater while the patients were intubated, and infusions of study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater. The patients were intubated and ventilated with oxygen-enriched air to attain acceptable arterial blood gases, and extubation occurred when clinically indicated. All patients received supplemental oxygen after extubation, which was delivered by a fixed performance device. Assessment of pain was by direct communication with the patient. comparisons. Of the 40 patients who participated in the study, seven patients could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. Consequently, data from 33 patients are used in the analysis of respiratory function; 16 received dexmedetomidine and 17 placebo. Inadequate arterial blood gas analysis was available in five patients (two from the dexmedetomidine group, and three from the placebo group). There were no significant differences in patient characteristics and operative details between the groups. = 0.040). ) for the 6 h after extubation. ). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group. Respiratory rate for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation. ) for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation. ratio for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation. ]. were mildly decreased and increased, respectively. There was a rightward shift and depression of the hypercapnic response with infusions of 1.0 and 2.0 μg/kg. between the groups. We can not therefore determine from this study whether dexmedetomidine has any benefits over morphine from a respiratory perspective. analysis reveals that the data have 80% power to detect a significant difference (α value 0.05). Further studies are obviously required. ] that dexmedetomidine provides cardiovascular stability, with a reduction in rate-pressure product over the extubation period. A sedative agent that has analgesic properties, minimal effects on respiration and offers ischaemia protection would have enormous potential in the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that are sufficient to provide adequate sedation and effective analgesia in the surgical population requiring intensive care.

Introduction:

]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period.

-mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved.

]) after extubation in the ICU.

Methods:

Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation.

] of 3 or greater while the patients were intubated, and infusions of study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater.

The patients were intubated and ventilated with oxygen-enriched air to attain acceptable arterial blood gases, and extubation occurred when clinically indicated. All patients received supplemental oxygen after extubation, which was delivered by a fixed performance device. Assessment of pain was by direct communication with the patient.

comparisons.

Results:

Of the 40 patients who participated in the study, seven patients could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. Consequently, data from 33 patients are used in the analysis of respiratory function; 16 received dexmedetomidine and 17 placebo. Inadequate arterial blood gas analysis was available in five patients (two from the dexmedetomidine group, and three from the placebo group). There were no significant differences in patient characteristics and operative details between the groups.

= 0.040).

) for the 6 h after extubation.

). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group.

Respiratory rate for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.

) for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.

ratio for the 6-h periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.

Discussion:

].

were mildly decreased and increased, respectively. There was a rightward shift and depression of the hypercapnic response with infusions of 1.0 and 2.0 μg/kg.

between the groups. We can not therefore determine from this study whether dexmedetomidine has any benefits over morphine from a respiratory perspective.

analysis reveals that the data have 80% power to detect a significant difference (α value 0.05). Further studies are obviously required.

] that dexmedetomidine provides cardiovascular stability, with a reduction in rate-pressure product over the extubation period. A sedative agent that has analgesic properties, minimal effects on respiration and offers ischaemia protection would have enormous potential in the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that are sufficient to provide adequate sedation and effective analgesia in the surgical population requiring intensive care.

Introduction

]. Cardiovascular stability was demonstrated with significant reductions in rate-pressure product during sedation and over the extubation period.

-mediated reduction in sympathetic tone. It should therefore be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved. After extubation dexmedetomidine can continue to provide analgesia to the postoperative patient, thus reducing the need for opioids and their side effects.

], and only data from our centre has been included.

Statistical analysis

comparisons were made using the Bonferroni test to determine differences among groups at individual time points, as well as differences over time within individual groups.

between the two groups (α value 0.05, β value 0.8).

Results

Of the 40 patients who participated in the study, seven could not be included in the analysis of respiratory function because they did not receive a study drug infusion after extubation. One patient required ventilation for longer than 24 h, and five patients were withdrawn from the study before extubation: two patients returned to the operating theatre because of bleeding; one had residual neuromuscular blockade; one had bradycardia with hypotension requiring a pacemaker; and one was withdrawn at the surgeon's request because of operative complications. A further patient had the study drug discontinued in error before extubation.

).

). In the dexmedetomidine group 50% (eight out of 16) patients required no morphine at all after extubation, compared with 24% (four out of 17) in the placebo group.

).

). There were no adverse respiratory events seen in either the dexmedetomidine or placebo group.

Requirements for rescue analgesia with morphine during the extubation period for patients receiving dexmedetomidine and placebo. Values are medians; boxes indicate 25-75th percentiles and bars indicate the range.

Oxygen saturation measured by pulse oximetry for the 6-h periods before and after extubation. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.

Arterial pH for the 6 hour periods before and after extubation, and baseline values (B) on admission to ICU immediately after surgery. (Filled circle) Dexmedetomidine; (Empty circle) placebo. Values are expressed as mean ± standard deviation.

Patient characteristics and operative details for the dexmedetomidine and placebo groups

Values are expressed as mean ± standard deviation or as numbers, unless otherwise stated. APACHE, Acute Physiology and Chronic Health Evaluation.

Discussion

The present results show that dexmedetomidine appears to have no clinically important adverse effects on respiratory rate and gas exchange when used in spontaneously breathing ICU patients after surgery.

].

.

were mildly decreased and increased, respectively, in relation to the depth of sedation as a result of dexmedetomidine infusions of 1.0 and 2.0 μg/kg. The reduction in minute ventilation was predominantly a result of a reduction in tidal volume, although there was a small but nonsignificant reduction in respiratory rate. There was a rightward shift and depression of the hypercapnic response at these infusion doses.

]. However, the effects of dexmedetomidine on human respiration are much less marked than those of opioids and other intravenous and volatile anaesthetic agents, and appear to be similar in order of magnitude to those seen in the heavy sleep state.

Previous studies that investigated the respiratory effects of dexmedetomidine have only been performed in healthy human volunteers, who have received either single intramuscular injections or short (≤ 10 min) intravenous infusions of dexmedetomidine. It is therefore reassuring that no deleterious clinical effects on respiration and gas exchange were seen in our patients, who received long-term infusions of dexmedetomidine.

between the groups. We can not therefore determine from the present study whether dexmedetomidine has any benefits over morphine from a respiratory perspective.

-adrenoceptor agonists.

]. A sedative agent that has analgesic properties, minimal effects on respiration and may offer ischaemia protection would also have enormous potential outside the ICU. Dexmedetomidine may fulfill all of these roles, but at present we can only conclude that dexmedetomidine has no deleterious clinical effects on respiration when used in doses that provide adequate sedation and effective analgesia in the surgical population requiring intensive care.

Acknowledgement

This study was supported by Abbott Laboratories. The results of this study were presented in part at the 20th International Symposium on Intensive Care and Emergency Medicine, Brussels, 2000.

Keywords

• α2-Adrenoceptor agonist
• analgesia
• dexmedetomidine
• intensive care
• postoperative
• respiratory
• sedation