Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation.
BACKGROUND
Interruption of sedation during weaning from mechanical ventilation often leads to patient agitation because of withdrawal syndrome. We tested the short-term efficacy and tolerance of loxapine in this situation.


METHODS
Nineteen mechanically ventilated patients with marked agitation after sedation withdrawal were included. Three agitation scales, the Richmond Agitation Sedation Scale (RASS), the Motor Activity Assessment Scale (MAAS), and the Ramsay and physiological variables (respiratory rate, airway occlusion pressure during the first 0.1 second of inspiration (P0.1), heart rate and systolic arterial blood pressure) were recorded before and after loxapine administration.


RESULTS
Loxapine dramatically improved all agitation scores (RASS and MASS decreased from 2 +/- 0 to -1.1 +/- 2.3, and 5.4 +/- 0.5 to 2.7 +/- 1.6, respectively; Ramsay increased from 1.0 +/- 0 to 3.5 +/- 1.5, 60 minutes after loxapine administration, P < 0.05 for all scores) as well as P0.1 (6 +/- 4.2 to 1.8 +/- 1.8 cm H2O; P < 0.05) and respiratory rate (from 31.2 +/- 7.2 to 23.4 +/- 7.8; P < 0.05) without hemodynamic adverse events. No side effects occurred. Sixteen (84%) patients were successfully managed with loxapine, sedation was resumed in two others, and one patient self-extubated without having to be reintubated.


CONCLUSIONS
Loxapine was safe and effective in treating agitation in a small group of mechanically ventilated patients and improved respiratory physiologic parameters, enabling the weaning process to be pursued. A multicenter trial is under way to confirm these promising results.
Sztrymf
Benjamin
B
Service de réanimation médicale, Hôpital Louis-Mourier, Assistance Publique-Hôpitaux de Paris, Université Denis Diderot, 178 rue des Renouillers 92701 Colombes Cedex, France. benjamin.sztrymf@abc.aphp.fr
Chevrel
Guillaume
G
Bertrand
Fabrice
F
Margetis
Dimitri
D
Hurel
Dominique
D
Ricard
Jean-Damien
JD
Dreyfuss
Didier
D
D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D008152:Loxapine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011595:Psychomotor Agitation / Q000188:drug therapy*; D015656:Respiratory Mechanics / Q000187:drug effects*; D012720:Severity of Illness Index; D015300:Ventilator Weaning / Q000523:psychology*
D014150:Antipsychotic Agents; D008152:Loxapine
Intensive Care Med. 2009 Feb;35(2):275-81
18709354
Chest. 2001 Dec;120(6 Suppl):375S-95S
11742959
Chest. 2005 Oct;128(4):2749-57
16236951
Lancet. 2009 Jan 3;373(9657):31-41
19058842
Intensive Care Med. 2001 Dec;27(12):1892-900
11797025
J Psychiatry Neurosci. 1996 Jan;21(1):29-35
8580115
JAMA. 2009 Feb 4;301(5):489-99
19188334
Am J Med. 1974 Aug;57(2):161-70
4843890
N Engl J Med. 2003 May 1;348(18):1786-95
12724485
Crit Care. 2009;13(3):R75
19454032
Neurocrit Care. 2007;7(2):124-7
17846719
N Engl J Med. 2000 May 18;342(20):1471-7
10816184
Intensive Care Med. 2004 May;30(5):830-6
15127195
Crit Care Med. 1999 Jul;27(7):1271-5
10446819
Intensive Care Med. 2007 Jan;33(1):66-73
17102966
Br Med J. 1974 Jun 22;2(5920):656-9
4835444
Intensive Care Med. 2004 Jun;30(6):1066-72
14966671
Eur Respir J. 2007 May;29(5):1033-56
17470624
Crit Care Med. 2004 Apr;32(4):955-62
15071384
N Engl J Med. 2008 Mar 27;358(13):1327-35
18367735
Crit Care. 2007;11(3):214
17521456
Crit Care Med. 1998 Apr;26(4):676-84
9559604
Intensive Care Med. 2004 Mar;30(3):444-9
14685663
J Appl Physiol (1985). 1993 Apr;74(4):1475-83
8514660
JAMA. 2004 Apr 14;291(14):1753-62
15082703
Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903
11934711
CNS Drugs. 2009;23(7):615-25
19552488
Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44
12421743
JAMA. 1993 Dec 22-29;270(24):2957-63
8254858
Crit Care Med. 2002 Jan;30(1):119-41
11902253