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Drug therapy for preventing post-dural puncture headache

  1. Xavier Basurto Ona1,*,
  2. Sonia Maria Uriona Tuma2,
  3. Laura Martínez García3,
  4. Ivan Solà3,
  5. Xavier Bonfill Cosp4

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 15 OCT 2012

DOI: 10.1002/14651858.CD001792.pub3


How to Cite

Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD001792. DOI: 10.1002/14651858.CD001792.pub3.

Author Information

  1. 1

    Hospital de Figueres, Fundació Salut Empordà, Emergency Department, Figueres, Girona-Catalunya, Spain

  2. 2

    Vall Hebron University Hospital, Preventive Medicine and Public Health, Barcelona, Catalunya, Spain

  3. 3

    Institute of Biomedical Research (IIB Sant Pau), Iberoamerican Cochrane Centre, Barcelona, Catalunya, Spain

  4. 4

    CIBER Epidemiología y Salud Pública (CIBERESP), Spain - Universitat Autònoma de Barcelona, Iberoamerican Cochrane Centre - Institute of Biomedical Research (IIB Sant Pau), Barcelona, Catalonia, Spain

*Xavier Basurto Ona, Emergency Department, Hospital de Figueres, Fundació Salut Empordà, Rda Rector Aroles s/n, Figueres, Girona-Catalunya, 17600, Spain. basurto18@gmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Abboud 1992

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: US (Los Angeles)

Setting: hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: double-blind

Follow-up period: 3 days


ParticipantsRandomised: 82 (intervention group: 40; control group: 42)

Excluded (post-randomisation): not described

Gender (women): 82 (100%)

Age (years): mean (SD): intervention group: 30.3 (6.3); control group: 29.6 (5.8)

Inclusion criteria: healthy pregnant women at term, ASA I or II with no medical complications, who underwent caesarean delivery with spinal anaesthesia

Exclusion criteria: not described


InterventionsIntervention group: intraspinal administration of morphine 0.2 mg in 0.2 mL solution

Control group: intraspinal administration of 0.2 mL of normal saline

Co-interventions: spinal anaesthesia with 0.75% bupivacaine in 8.25% dextrose plus 0.2 mL of 1:1000 epinephrine. Hydration with 1500 mL lactated Ringer's solution


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of any possible adverse effects from the drug taken to prevent PDPH


NotesPDPH defined as: quote: "PDPH if it occurred after the patient became ambulatory, was aggravated by sitting or standing position, was relieved by lying supine, and was mostly occipital or frontal" (Page 34)

Sample size calculation: quote: "Consultation with a statistician determined the sample size of the study. The statistical approach was analysed to ensure that the power of these data was adequate to decrease below the level of statistical probability that a Type II error could have been made" (Page 35)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information provided. Quote: "Patients were randomly assigned to receive, in a double-blind fashion, either 0.2 mg of morphine (Group 1, n = 40) or saline (Group 2, n = 42)..."

Allocation concealment (selection bias)Unclear riskNo information available

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information available

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information available

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults presented for all 82 randomised patients

Selective reporting (reporting bias)Unclear riskNo information available

Al-metwalli 2008

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: Saudi Arabia (Al-Khobar)

Setting: hospital

Study design: parallel

Randomisation: computer-generated random number table

Allocation concealment: opaque envelope labelled with the study subject number

Blinding: double-blind

Follow-up period: minimum 5 days in those without PDPH and 3 days after resolution of the headache in those with PDPH


ParticipantsRandomised: 50 (intervention group: 25, control group: 25)

Excluded (post-randomisation): not described

Gender (women): 50 (100%)

Age (years): mean (SD): intervention group 28.4 (6.0); control group 29.6 (5.4)

Inclusion criteria: postpartum woman with inadvertent dural puncture during epidural analgesia in labour

Exclusion criteria: temperature > 37.8 ºC, coagulopathy and delivering by caesarean section


InterventionsIntervention group: epidural morphine 3 mg in 10 mL saline and repeated the same treatment after 24 h

Control group: epidural 10 mL saline and repeated the same treatment after 24 h

Co-interventions: 3 mL of lidocaine 2% with fentanyl 15 μg administered to all patients before delivery to test correct epidural placement. Next, 10 mL bupivacaine 0.25% with 50 μg of fentanyl  was injected followed by a continuous infusion of bupivacaine 0.125% with 1 μg/mL of fentanyl at 10 mL/h


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of participants with severe PDPH
  • Number of any possible adverse effects from the drug taken to prevent PDPH


NotesPDPH defined as: quote "PDPH was defined as the presence of a headache or neck ache that improved significantly or completely when the subject assumed the supine position"

Sample size calculation: 24 participants calculated estimating an incidence decrease of PDPH from 75% to 35%. Significance level of 0.05 and power of 80%

VRSP: 0 = no pain and 10 = worst possible pain


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomised (via a computer-generated random number table) to treatment (morphine) group or control (saline) group" (Page 848)

Allocation concealment (selection bias)Low riskQuote: "Group assignment was determined by opening an opaque envelope labelled with the study subject number" (Page 848)

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "An anaesthetist, who was blind to the study drug, injected 10 ml saline (control group) or 3 mg of morphine in 10 ml saline (morphine group)" (Page 848)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "An anaesthetist unaware of the treatment group evaluated the subjects postpartum to ascertain the presence of PDPH" (Page 848)

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults presented for all 50 randomised patients

Selective reporting (reporting bias)Low riskResults presented according to objectives stated in the introductory section

Devcic 1993

MethodsRandomised, blinded, controlled trial

Study type: single-centre study

Location: US (Milwaukee)

Setting: hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: blinding of patients and outcome assessors

Follow-up period: 3 weeks


ParticipantsRandomised: 194 (Sprotte needle with fentanyl: 47; Sprotte needle without fentanyl: 49; Quincke needle with fentanyl: 49; Quincke needle without fentanyl: 49)

Excluded (post-randomisation): not described

Gender (women): 194 (100%)

Age (years): mean (SD): Sprotte needle with fentanyl: 28.2 (5.8); Sprotte needle without fentanyl: 29.5 (4.4); Quincke needle with fentanyl: 28.3 (5.6), Quincke needle without fentanyl: 28.7 (5.5)

Inclusion criteria: healthy obstetric patients requiring caesarean delivery who consented to spinal anaesthesia

Exclusion criteria: previously attempted or performed labour epidural analgesia or spinal anaesthesia attempted with other kind of needles


InterventionsIntervention group: subarachnoid  fentanyl 20 μg through a 24-gauge Sprotte needle or through a 25-gauge Quincke needle

Control group: subarachnoid anaesthesia without fentanyl through a 24-gauge Sprotte needle or through a 25-gauge Quincke needle

Co-interventions: all patients received 1000 to 1500 mL of 0.9% normal saline or Ringer's lactate solution before spinal anaesthesia and continued for 48 h

Spinal anaesthesia with hyperbaric bupivacaine 0.75% to all patients. The total dose was decided by the anaesthesiologist performing the spinal anaesthesia

Opioids via patient–controlled pump during the first 24 h postoperative and followed the next day by oral analgesics as needed


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of participants with severe PDPH
  • Number of missing data (withdrawals, drop-outs and participants lost to follow-up)


NotesPDPH defined as: quote: "If the headache occurring on mobilization was aggravated by an erect position and was relieved by lying flat, it was considered to be a PDPH" (Page 223)

Sample size calculation: not described

PDPH severity: mild (annoying, but tolerable on ambulation, requiring oral analgesics); moderate (very annoying, very uncomfortable on ambulation, requiring bed rest, scheduled analgesia with intravenous fluids); severe (bedridden requiring EBP)

Email contact


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information provided

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskDescribed as blinded

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All patients were evaluated daily during the first 4 postoperative days by the designated nurse, who was blinded to the type of needle and medication used... Investigators conducting telephone follow-up were blinded to the type of needle and anaesthetic solution used" (Page 223)

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk6 lost to follow-up described (4 in fentanyl group, 2 in control group), but is unlikely that this loss may influence the outcomes

Selective reporting (reporting bias)High riskAdverse events not reported

Doroudian 2011

MethodsRandomised, blinded, controlled trial

Study type: single-centre study

Location: Iran (Kerman)

Setting: admitted to hospital

Study design: parallel

Randomisation: computer-generated random allocation

Allocation concealment: not described

Blinding: blinding of patients and the spinal anaesthesia staff

Follow-up period: 7 days


ParticipantsRandomised: 178 (intervention group: 89; control group: 89)

Excluded (post-randomisation): none

Gender (women): 61 (34.3%)

Age (years): mean (range): intervention group 41.7 (31 to 53); control group 40 (30 to 50)

Inclusion criteria: all adults admitted to hospital for lower-extremity surgery

Exclusion criteria: hypo/hypertension, diabetes, dexamethasone intolerance or past hypersensitivity reaction, intake of any analgesic or anti-inflammatory agent during the week prior to admission, past history of chronic headache, recent-onset acute headache, contraindication for LP, a surgical procedure estimated to last longer than 90 minutes, current pregnancy, past/active peptic ulcer disease, active systemic fungal infection, any kind of addiction, more than 2 attempts at spinal anaesthesia, any history of cardiopulmonary disorder, long-term admission, severe post-spinal haemodynamic changes and strong dependency to tea or caffeine


InterventionsIntervention group: intravenous dexamethasone 8 mg (2 mL) of before spinal anaesthesia

Control group: 2 mL of intravenous normal saline before spinal anaesthesia

Co-interventions: all patients received 500 mL of normal saline intravenously before intervention and spinal anaesthesia


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of participants with severe PDPH
  • Number of missing data (withdrawals, drop-outs and participants lost to follow-up)


NotesPDPH defined as: an exclusion criteria was: quote: "long term admission which does not permit patient to resume the upright position within the first 7 days" (Page 144) and Class I intensity headache was: quote: "Patient suffers from a mild headache while sitting or walking" (Page 144)

Sample size calculation: not described

PDPH severity:

Class I: "Patient suffers from a mild headache while sitting or walking", Class II: "Patient suffers from a moderate to severe headache while sitting or walking" and Class III: "Patient suffers from a moderate to severe headache even in supine position which impedes his/her daily activities"


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The randomization process was performed using Random Allocation Software®" (Page 143)

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "For all injections, the anesthetic staff was blind with respect to the group allocation whereas patients were also unaware regarding the content of the study injectate" (Page 144)

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults presented for all 178 randomised patients

Selective reporting (reporting bias)High riskAdverse events not reported

Esmaoglu 2005

MethodsRandomised, blinded, controlled trial

Study type: single-centre study

Location: Turkey (Kayseri)

Setting: admitted to hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: outcome assessors and probably patients

Follow-up period: 7 days


ParticipantsRandomised: 210 (caffeine 75 group: 70; caffeine 125 group: 70; control group: 70)

Excluded (post-randomisation): not described

Gender (women): 83 (39.5%)

Age (years): mean (SD): caffeine 75 group: 38 (12); caffeine 125 group: 38 (11); control group: 37 (14)

Inclusion criteria: patients scheduled for elective lower extremity surgery, ASA I-II

Exclusion criteria: hypertension, diabetes mellitus, caffeine consumption > 250 mg/day, intolerance to caffeine, chronic headache, contraindication to spinal anaesthesia


InterventionsCaffeine 75 group: paracetamol 500 mg + caffeine 75 mg orally

Caffeine 125 group: paracetamol 500 mg + caffeine 125 mg orally

Control group: placebo orally

All 3 groups received intervention 1 h before the spinal anaesthesia and the same doses repeated every 6 hours for 3 days. Spinal anaesthesia with 3 mL of hyperbaric bupivacaine 0.5%

Co-interventions: all patients hydrated with at least 0.5 L of intravenous crystalloid solution before the procedure


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of participants with severe PDPH
  • Number of participants with any headache
  • Number of any possible adverse effects from the drug taken to prevent PDPH


NotesPDPH defined as: quote: "headache was categorized as a PDPH if it was worse on sitting or standing and relieved or reduced by lying flat" (Page 59)

PDPH severity: quote: "class I, mild headache when sitting or ambulating; class II, moderate to severe headache when sitting or ambulating; and class III, moderate to severe headache when supine" (Page 60)

Sample size calculation: not described


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information provided

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The interviewer was blinded as to study group assignment" (Page 59)

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo explicit information but it seems that no patients were lost

Selective reporting (reporting bias)Unclear riskNo information available

Flaatten 1987

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: Norway (Bergen)

Setting: admitted to hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: double-blind

Follow-up period: 3 days


ParticipantsRandomised: 250 (intervention group: 125; control group: 125)

Excluded (post-randomisation): not described

Gender (women): 85 (34%)

Age (years): mean: intervention group 34.2; control group 33.0

Inclusion criteria: young (< 55 years old) hospitalised patients of either sex of ASA groups I and II, receiving spinal anaesthesia

Exclusion criteria: not described


InterventionsIntervention group: indomethacin 100 mg per rectum 4 hours post operation

Control group: placebo per rectum 4 hours post operation

Co-interventions: all spinal anaesthesia were performed using a 25-G spinal needle


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of missing data (participants lost to follow-up)


NotesPDPH defined as: quote "occurred after mobilisation, aggravated by the erect or sitting position, relieved by lying flat, mostly occipital or frontal, accompanied by dizziness, vomiting, rigidity of the neck and visual disturbances" (Page 202)

Sample size calculation: not described


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information provided. Quote: "following this they were randomly allocated in a double-blind manner to receive either indomethacin 100mg or a placebo per rectum 4 hours postoperatively" (Page 202)

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "Three patients were lost to follow-up and their results are not included in the study." (Page 202). All 3 patients from placebo group, and not reasons stated. Unlikely to produce bias, but incomplete information available

Selective reporting (reporting bias)Unclear riskNo information available

Hakim 2010

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study
Location: Egypt (Cairo)

Setting: admitted to hospital

Study design: parallel

Randomisation: computer-generated random number list

Allocation concealment: yes

Blinding: blinding of patients, hospital health personnel and outcome assessors

Follow-up period: 14 days


ParticipantsRandomised: 95 (intervention group: 47; control group: 48)

Excluded (post randomisation): 5 (intervention group: 2; control group: 3)

Gender (women): 95 (100%)

Age (years): mean (SD): intervention group: 31.3 (4.8); control group: 29.7 (4.9)

Inclusion criteria: parturients who had epidural analgesia for normal vaginal delivery and who suffered an inadvertent dural tap

Exclusion criteria: contraindication to steroid or ACTH therapy (e.g. hypertension or diabetes mellitus), pre-eclampsia, or contraindication to EBP (e.g. fever or leukocytosis)


InterventionsIntervention group: cosyntropin 1 mg (Cortrosy®, Amphastar Pharmaceuticals Inc) in 1 mL solution, intravenously over 5 min

Control group: 1 mL of normal saline intravenously

Co-interventions: epidural analgesia: test with 3 mL of 2% lidocaine with 1:200,000 epinephrine. Loading dose of 8 to 15 mL of bupivacaine 0.125% plus fentanyl 50 μg. Continuous infusion of bupivacaine 0.125% with fentanyl 2 μg/mL at 8 to 15 mL/h. Patients with accidental dural puncture were encouraged to ambulate and to drink plenty of fluids, with prescription of stool softeners


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of any possible adverse effects from the drug taken to prevent PDPH
  • Number of missing data (withdrawals, drop-outs and participants lost to follow-up)


NotesPDPH defined as: quote: "PDPH if they developed headache within 5 days after dural puncture, which worsened within 15 min of sitting or standing, and improved within 15 min after lying, with at least one of the following criteria: neck stiffness, tinnitus, hypacusia, photophobia, or nausea" (Page 414)

Sample size calculation: estimated 44 patients in each group for detecting at least a 30% difference between the groups the incidence of PDPH, a beta error of 0.2, 2-tailed alfa-error of 0.05 and degree of freedom of 1


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned to one of two groups using a computer-generated random number list. The list was created using the GraphPad StatMate version 1.01i software" (Page 414)

Allocation concealment (selection bias)Low riskQuote: "The list... was accessible to anaesthesiologist attending to patients in labor through the computer database" (Page 414)

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Injections were prepared by assistants not participating in the study, and both the patients and those involved in the study were blinded as to the patients' group" (Page 414)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Nurses and anaesthesiologists involved in headache assessment were blinded as to the patients' group" (Page 414)

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Flowchart showing incidence of accidental dural puncture, patient recruitment and randomisation, incidence of PDPH and need for EBP and repeat EBP" (Page 415)

Selective reporting (reporting bias)Low riskResults presented according to objectives stated in the introductory section

Sadeghi 2012

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: Iran (Shiraz)

Setting: admitted to hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: double-blind (patient and researcher)

Follow-up period: 48 hours after elective caesarean section


ParticipantsRandomised: 120 (intervention group: 60; control group: 60)

Excluded (post-randomisation): not described

Gender (women): 120 (100%)

Age (years): mean (SD): intervention group 26.11 (4.4); control group 26.35 (5.3)

Inclusion criteria: patients undergoing elective caesarean section

Exclusion criteria: headache, psychiatric problems, back pain, pre-eclampsia, coagulation disorders, convulsion background, spinal anaesthesia history and those who used any kinds of opiates


InterventionsIntervention group: after the child birth and umbilical cord clamping, aminophylline 1 mg/kg intravenously

Control group: no intervention

Co-interventions: 2 mL lidocaine 1% used for skin anaesthesia. A combination of 55 mg lidocaine 5% (dose and concentration as cited in the publication) and meperidine 5 mg were used for spinal anaesthesia. Needle nº 23 used for the spinal anaesthesia. In case of hypotension in both groups, ephedrine 5 mg intravenously. In both groups, the patients rested 24 h after the operation and then started walking


Outcomes
  • Number of participants affected by PDPH of any severity


NotesPDPH defined as: quote "Post dural puncture headache (PDPH) is a kind of headache that worsens by standing up and dwindles with recumbency" (Page 13)

Sample size calculation: not described


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomly divided into two groups with an accidental allocation" (Page 14)

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "double-blind randomised study (patient and researcher)" (Page 14)

Quote: "data collection performed by a trained nurse that did not know anything about the intervention, the other stages of the study were performed by the doctors who knew the whole project and it may cause bias in the study" (Page 15)

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "data collection performed by a trained nurse that did not know anything about the intervention, the other stages of the study were performed by the doctors who knew the whole project and it may cause bias in the study" (Page 15)

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo explicit information but it seems that no patients were lost

Selective reporting (reporting bias)High riskAdverse events not reported

Strelec 1994

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: US (Pittsburgh)

Setting: hospital

Study design: parallel

Randomisation: not described

Allocation concealment: not described

Blinding: described as double-blind

Follow-up period: 4 days


ParticipantsRandomised: 60 (intervention group: 30; control group: 30)

Excluded (post randomisation): 2 (intervention group: 0; control group: 2)

Gender (women): 18 (31%)

Age (years): mean (SD): intervention group: 40.2 (13.3); control group: 48.5 (13)

Inclusion criteria: participants who have had a lumbar myelography

Exclusion criteria: not described


InterventionsIntervention group: oral anhydrous caffeine capsules, 300 mg every 8 hours for 3 days

Control group: placebo capsules every 8 hours for 3 days

Co-interventions: all other caffeinated substances were forbidden


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of any possible adverse effects from the drug taken to prevent PDPH
  • Number of missing data (withdrawals, drop-outs and participants lost to follow-up)


NotesPDPH defined as: quote: "PDPH criteria included postural headache, associated N/V, photophobia and neck stiffness" (Page 79)

Sample size calculation: not described


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information provided

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk2 lost. No information provided about the reasons or the moment, but unlikely this is a cause of bias

Selective reporting (reporting bias)Low riskResults presented according to objectives stated in the introductory section

Yousefshahi 2012

MethodsRandomised, double-blind, controlled trial

Study type: single-centre study

Location: Iran (Tehran)

Setting: admitted to hospital

Study design: parallel

Randomisation: computer-generated random number list

Allocation concealment: not described

Blinding: described as double-blind

Follow-up period: 3 days


ParticipantsRandomised: 372 (intervention group: 186; control group: 186)

Excluded (post randomisation): 12 (intervention group: 4; control group: 8)

Gender (women): 372 (100%)

Age (years): mean: intervention group: 28.5; control group: 28.9

Inclusion criteria: parturient after spinal anaesthesia for caesarean section

Exclusion criteria: patients ASA class higher than II, sensitive to local anaesthetics, anticoagulant therapy, pre-eclampsia or skin infection at the site of needle insertion


InterventionsIntervention group: intravenous dexamethasone 8 mg (2 mL) after clamping the umbilical cord

Control group: 2 mL of intravenous normal saline after clamping the umbilical cord

Co-interventions: all patients received 500 mL of normal saline or Ringer's solution intravenously before spinal anaesthesia. Ondansetron, metoclopramide and H2-blockers as needed


Outcomes
  • Number of participants affected by PDPH of any severity
  • Number of participants with severe PDPH
  • Number of participants with any headache
  • Number of missing data (withdrawals, drop-outs and participants lost to follow-up)


NotesPDPH defined as: quote: "PDPH was defined as a headache located in the occipital and/or frontal areas which was worsened by standing or sitting, and alleviates by lying down" (Page 2)

Sample size calculation: quote: "The study was designed to achieve 80 % power to detect a 15 % difference in the population, in which the prevalence of the condition was 8.9 % based on previous studies. The level of statistical significance was reported to be 5 %" (Page 3)

Email contact with Fardin Yousefshahi MD on April 2012 for clarification about missing data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were divided into two groups based on a computer random number generator" (Page 2)

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Each patient received a specific row number for grouping into the dexamethasone or placebo group, corresponding to a computerized randomization system; grouping was not reflected in the patient’s data sheet" (Page 2)

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Trained nurses, who were unaware of the objectives of the study, asked the patients about any occurrence of headache every 24 h for 72 h. The patients complaining of possible PDPH were then visited by an anesthesiologist, similarly unaware of the study objectives, to rule out other causes of headache" (Page 2)

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Twelve patients were excluded from the study due to missing data" (Page 2). 4 patients from the intervention group and 8 from the control group

Selective reporting (reporting bias)Low riskResults presented according to objectives stated in the introductory section

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ackerman 2004No individual drug assessed

Altunkaya 2005The study did not focus on PDPH

Aziz 1968The orthostatic component of headache not described

Balestrieri 2003The study was not a RCT (letter)

Beilin 2003The orthostatic component of headache not described

Breebaart 2003The study did not focus on PDPH

Caldwell 1994The orthostatic component of headache not described

Camann 1992The orthostatic component of headache not described

Camann 1993The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Campbell 1995The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Cesur 2009The study was not a RCT (retrospective observational study)

Chalmers 1988The study did not focus on PDPH

Intervention was not aimed at preventing PDPH

Chilvers 1997Intervention was not aimed at preventing PDPH

Cho 2008The study did not focus on PDPH

Clarke 2009The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Colonna-Romano 1989No individual drug assessed

Cowan 1980The orthostatic component of headache not described

D'Angelo 1994The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Danelli 2004The study did not focus on PDPH

Dayioglu 2009The orthostatic component of headache not described

De Pietri 2006The orthostatic component of headache not described

Delfino 2001The orthostatic component of headache not described

Dijkstra 2008The orthostatic component of headache not described

Intervention was not aimed to prevent PDPH

Dilli 2008The study did not focus on PDPH

Dominguez-Hervella 1993The orthostatic component of headache not described

Edström 1986The orthostatic component of headache not described

Elkhodair 2010The study was not a RCT (Critically Appraised Topics)

Fogarty 1993The study did not focus on PDPH

Fogarty 1995The study did not focus on PDPH

Frey 1998The orthostatic component of headache not described

Frizelle 1997The orthostatic component of headache not described

Fu 2008The study did not focus on PDPH

Fujii 1998The study did not focus on PDPH

Förster 2006The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Gangopadhyay 2010The orthostatic component of headache not described

Ganzi 1995No individual drug assessed

Garg 2010The study did not focus on PDPH

Gielen 1986The study did not focus on PDPH

Ginsberg 1996The study did not focus on PDPH

Girgin 2008The study did not focus on PDPH

Gogarten 2004The study did not focus on PDPH

Gurbet 2008The study did not focus on PDPH

Hansen 1979The orthostatic component of headache not described

Hansen 1980The study was not a RCT (letter)

Harsten 1997The orthostatic component of headache not described

Hein 2010The orthostatic component of headache not described

Hendriks 2009The orthostatic component of headache not described

Ilioff 1990The orthostatic component of headache not described

Imbelloni 2003The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Imbelloni 2009Intervention was not aimed at preventing PDPH

Imbelloni 2010The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Jacobsohn 2005The orthostatic component of headache not described

Kallio 2004The study did not focus on PDPH

Kallio 2005The study did not focus on PDPH

Kaukinen 1981Allocation was not randomised

Kouri 2004The study did not focus on PDPH

Lanz 1982The study did not focus on PDPH

Lauretti 1999The study did not focus on PDPH

Lauretti 1999bThe study did not focus on PDPH

Lauretti 2000The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Lauretti 2000bThe study did not focus on PDPH

Lee 2005The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Lewis 1992The study did not focus on PDPH

Lierz 2004The study did not focus on PDPH

Luck 2008The study did not focus on PDPH

López-Soriano 2002The orthostatic component of headache not described

Manaa 2005The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Martlew 2009The study was not a RCT (letter)

Massou 2008The study was not a RCT (letter)

Meininger 2003The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Michalek-Sauberer 2008The orthostatic component of headache not described

Morrison 1994The study did not focus on PDPH

Mosavy 1975Allocation was not randomised

Murto 1999The orthostatic component of headache not described

Møller 1984The orthostatic component of headache not described

Neilson 2008The study did not focus on PDPH

Ogun 2003The study did not focus on PDPH

Paech 1993The orthostatic component of headache not described

Palahniuk 1979Allocation was not randomised

No individual drug assessed

Pan 2001The study did not focus on PDPH

Patra 2005The study did not focus on PDPH

Phero 1987The orthostatic component of headache not described

Plaja 2000The study did not focus on PDPH

Prusinski 1974Allocation was not randomised

Radpay 2003The study did not focus on PDPH

Reinhart 1985The study did not focus on PDPH

Rivera-Ordonez 2005The study did not focus on PDPH

Roux 1983The orthostatic component of headache not described

Rucci 1985The study did not focus on PDPH

Ryan 1983The study did not focus on PDPH

Sakaguchi 2000The study did not focus on PDPH

Sangarlangkarn 1987The orthostatic component of headache not described

Sanli 2005Intervention was not aimed at preventing PDPH

Santos 1986The study was not a RCT (no control group)

The orthostatic component of headache not described

Sawhney 2004The study did not focus on PDPH

Sengupta 1989No individual drug assessed

Seyhan 2005The study was not a RCT (no control group)

Shah 2003The study did not focus on PDPH

Singh 2006The study did not focus on PDPH

Smith 2004The study did not focus on PDPH

Soni 2001The study did not focus on PDPH

Sudarshan 1995The study did not focus on PDPH

Tekin 2007The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Thomas 2006The study did not focus on PDPH

Trivedi 1993Epidural saline infusion was not used as a pharmacological agent

Tsen 2001The orthostatic component of headache not described

Tucker 2004The study did not focus on PDPH

Tuncer 2005The study did not focus on PDPH

Turan 2006The study did not focus on PDPH

Turker 2003The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Unlugenc 2006The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Unlugenc 2009The orthostatic component of headache not described

Intervention was not aimed at preventing PDPH

Usubiaga 1967Allocation was not randomised

No individual drug assessed

Vaghadia 1997Intervention was not aimed at preventing PDPH

Vale 1995The study did not focus on PDPH

Vichitvejpaisal 1992Intervention was not aimed at preventing PDPH

Viscusi 2005The study did not focus on PDPH

Waxler 2004The study did not focus on PDPH

Wells 2004The study did not focus on PDPH

Whiteside 2003Intervention was not aimed at preventing PDPH

Widerlöv 1979The orthostatic component of headache not described

Wilder-Smith 1998The study did not focus on PDPH

Wood 1993The study did not focus on PDPH

Yanagidate 2004The study did not focus on PDPH

Yeh 2000The study did not focus on PDPH

Yücel 1999The orthostatic component of headache not described

Zackova 2000The study did not focus on PDPH

 
Comparison 1. Spinal morphine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of any possible adverse effects from the drug taken to prevent PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

    2.1 Pruritus
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Nausea and vomiting
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Epidural morphine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of participants with severe PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of any possible adverse effects from the drug taken to prevent PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

    3.1 Pruritus
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Nausea and vomiting
1Risk Ratio (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Spinal fentanyl versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of participants with severe PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of missing data (withdrawals, drop-outs and participants lost to follow-up)1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 4. Caffeine 75 mg versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of participants with severe PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of participants with any headache1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 5. Caffeine 125 mg versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of participants with severe PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of participants with any headache1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 6. Caffeine 75 mg versus caffeine 125 mg

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of participants with severe PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of participants with any headache1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 4 Number of any possible adverse effects from the drug taken to prevent PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 7. Indomethacin versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of missing data (withdrawals, drop-outs and participants lost to follow-up)1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 8. Cosyntropin versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of any possible adverse effects from the drug taken to prevent PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of missing data (withdrawals, drop-outs and participants lost to follow-up)1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 9. Caffeine 300 mg versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 2 Number of any possible adverse effects from the drug taken to prevent PDPH1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 3 Number of missing data (withdrawals, drop-outs and participants lost to follow-up)1Risk Ratio (IV, Fixed, 95% CI)Totals not selected

 
Comparison 10. Dexamethasone versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity2Risk Ratio (M-H, Random, 95% CI)Totals not selected

 2 Number of participants with severe PDPH2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Number of participants with any headache1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Number of missing data (withdrawals, drop-outs and participants lost to follow-up)2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 11. Caffeine versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1280Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.52, 1.59]

 2 Number of participants with severe PDPH1280Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.33, 2.35]

 3 Number of participants with any headache1280Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.51, 1.24]

 
Comparison 12. Aminophylline versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of participants affected by PDPH of any severity1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Number of participants affected by PDPH of any severity at 24 hours
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Number of participants affected by PDPH of any severity at 48 hours
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]