Sickle cell disease: high dose cetiedil may decrease the number of painful sites.

Clinical bottom line (level 1b-)

  1. Patients with sickle cell disease and painful crises who were given cetiedil 0.4 mg/kg body weight, may have a greater decrease in the number of painful sites, than those given placebo.
  2. Patients given 0.2 or 0.3 mg/kg had no clear difference in painful crises.
  3. Patients given 0.3 or 0.4 mg/kg had no clear difference in adverse effects.
Benjamin et al: Blood 1986; 67 (5): 1442-1447
Expires February 2003

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: five clinical centres, USA

67 patients (aged range 19 to 49 years; mean 27, 57% male) sickle cell disease (confirmed with electrophoresis) 4-24 hours after the onset of painful crises

Excluded if
  • < 19 years old
  • pregnant women and women of childbearing potential
  • incarcerated patients
  • patients with transfusion <90 days
  • history of drug abuse or dependency
  • acute cerebrovascular accident
  • overt infection
  • renal impairment (creatinine >180 mmol/dL)
  • clinical or roentgenographic evidence of pulmonary oedema
  • glaucoma
  • urinary retention
  • history of anti-cholinergic/ atropine-like hypersensitivity
  • incapable of giving informed consent


    • Control Group: (n = 18, 18 analysed): placebo- 0.9 mg/mL normal saline iv every 8 hours over 30 minutes fro 4 days
    Experimental Group: (n = 17, 17 analysed): 0.2 mg/kg cetiedil in normal saline iv every 8 hours over 30 minutes for 4 days
    Experimental Group: (n = 18, 18 analysed): 0.4 mg/kg cetiedil
    Experimental Group: (n = 14, 14 analysed): 0.6 mg/kg cetiedil
    All patients had fluid replacement therapy as required. They also had meperidine (1.2 mg/kg) or the equivalent morphine sulphate for severe pain, and oral acetaminophen (300 mg) with codeine phosphate (30 mg) for moderate pain.
    100% followed for 8 days
    Outcome notes:
    • adverse effects- 0.2 mg/kg : including dry mouth, nausea, vomiting, headache and drowsiness

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    adverse effects- 0.2 mg/kg 8 days 8
    (44.4%)    		 2
    (11.8%)    		 74.0%
    (-7.00% to 93.0%)    		 32.7%
    (5.08% to 60.3%)    		 3
    (2 to 20)

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    adverse effects- 0.3 mg/kg 8 days 8
    (44.4%)    		 9
    (50.0%)    		 -13.0%
    (-125% to 44.0%)    		 -5.56%
    (-38.1% to 27.0%)    		 18
    (NNT = 3 to infinity;
    NNH = 4 to infinity)

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    adverse effects- 0.4 mg/kg 8 days 8
    (44.4%)    		 8
    (57.1%)    		 -29.0%
    (-156% to 35.0%)    		 -12.7%
    (-47.3% to 21.9%)    		 -8
    (NNT = 2 to infinity;
    NNH = 5 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    change in number of painful sites- 0.2 mg/kg -1.5
    ()     		-1.25
    ()     		-0.25
    ( to )

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    change in number of painful sites- 0.3 mg/kg -1.50
    ()     		-2.00
    ()     		0.50
    ( to )

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    change in number of painful sites- 0.4 mg/kg -1.50
    ()     		-3.00
    ()     		-1.50
    ( to )

    Comments

    1. No confidence intervals or p-values were available for the number of painful sites. The painful sites results were read from a graph and were not detailed in the text.
    2. 0.3 mg/kg and 0.4 mg/kg of cetiedil said to shorten length of crisis (p<0.05) compared with placebo, but no figures were given in the text. From the chart in the paper, difference is 4 days vs 3.5 days- is this worthwhile.
    3. There is no difference noted in pain intensity by patients on cetiedel compared with placebo.
    4. The study is too small to comment about therapy benefits.
    5. Would anti-sickling agents be more useful in preventing crises rather than treating them?
    6. Investigators rate patients responses to cetiedel as excellent or good on more occasions than with placebo.

    Citation

    1. Benjamin LJ, Berkowitz LR, Orringer E, et al: A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis. Blood 1986; 67 (5): 1442-1447
    Contributor: Nick Shenker and Clare Wotton, February 2000
    Reviewer:

    Clinical Question.
    Patient sickle cell disease
    Intervention or Exposure cetiedil
    Comparison placebo
    Outcome painful sites