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 Table of Contents  
ORIGINAL RESEARCH REPORT
Year : 2020  |  Volume : 17  |  Issue : 2  |  Page : 13-19

Evaluation of prophylactic intravenous hydrocortisone for the prevention of postdural puncture headache following spinal anesthesia for cesarean section


1 Department of Anaesthesia, UCH, Ibadan, Nigeria
2 Department of Anaesthesia, University of Ibadan and UCH, Ibadan, Nigeria
3 Department of Obstetrics and Gynaecology, University of Ibadan and UCH, Ibadan, Nigeria

Date of Submission08-Nov-2019
Date of Acceptance11-Mar-2020
Date of Web Publication14-May-2020

Correspondence Address:
Dr. Alaba Olusola Ogunsiji
Department of Anaesthesia, University College Hospital, Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcls.jcls_71_19

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  Abstract 


Context: Postdural puncture headache (PDPH) is a common complication following spinal anesthesia. No medication is currently used on routine basis for its prevention despite its high incidence. Aims: This study evaluated the efficacy of prophylactic intravenous (IV) hydrocortisone 100 mg in reducing the incidence and severity of PDPH among obstetric patients who had spinal anesthesia for cesarean delivery. Study Design: This study is a double-blind, randomized controlled trial in which 400 consenting parturients having cesarean section under spinal anesthesia were randomized into two groups; hydrocortisone and control groups. Following delivery, patients in the hydrocortisone group received IV hydrocortisone 100 mg diluted to 2 ml while those in the control group received the same volume of 0.9% saline. Patients were reviewed for the occurrence of PDPH over 5 days and headache severity assessed using the numerical rating scale. Intraoperative and postoperative side effects of single-dose hydrocortisone were also documented. Statistical Analysis: Data were analyzed using SPSS 20 software. A P < 0.05 was considered statistically significant. Results: A total of 197 and 194 patients completed the study in the hydrocortisone and control groups, respectively. In the hydrocortisone group, 46 patients (23.4%) developed PDPH compared to 48 patients (24.7%) in the control group (P = 0.813). Both the mean maximum NRS scores as well as headache severity grades were similar between both groups with P = 0.930 and 0.714, respectively. The duration of PDPH averaged 2.87 ± 1.44 days in hydrocortisone group compared with 2.73 ± 1.38 days in control group (P = 0.630). Conclusions: Prophylactic IV hydrocortisone 100 mg does not reduce the incidence or severity of PDPH following spinal anesthesia for cesarean section.

Keywords: Headache, hydrocortisone, postdural puncture headache, Quincke needle


How to cite this article:
Ogunsiji AO, Osinaike BB, Amanor-Boadu SD, Obajimi GO. Evaluation of prophylactic intravenous hydrocortisone for the prevention of postdural puncture headache following spinal anesthesia for cesarean section. J Clin Sci 2020;17:13-9

How to cite this URL:
Ogunsiji AO, Osinaike BB, Amanor-Boadu SD, Obajimi GO. Evaluation of prophylactic intravenous hydrocortisone for the prevention of postdural puncture headache following spinal anesthesia for cesarean section. J Clin Sci [serial online] 2020 [cited 2020 Jul 12];17:13-9. Available from: http://www.jcsjournal.org/text.asp?2020/17/2/13/284279




  Introduction Top


The history of postdural puncture headache (PDPH) is as old as the history of spinal anesthesia itself, occurring in the very first patient who was given a spinal block by Dr. Karl August Bier on August 16, 1898 in Germany.[1] As far back as 1923, Herbert Greene reportedly associated spinal needle size and tip design with occurrence of PDPH.[2] The incidence of PDPH is lower for pencil point needles but with the prevalently used 25G Quincke spinal needle in the West African subregion and other developing nations, the incidence of PDPH ranges between 3% and 25%.[3] In Benin City, Nigeria, an incidence of 22.7% was found among obstetric patients given spinal anesthesia using 25G Quincke needles.[4]

Several drugs, including intravenous (IV) aminophylline, IV cosyntropin, and epidural morphine, have been used prophylactically to prevent the occurrence of PDPH following dural puncture.[5] Considerations of cost, the availability and side effects of these drugs limit their routine use in the setting of spinal anesthesia. Hydrocortisone has the advantage of being cheap, readily available and without significant side effects with short-term use.[6] It has also been used successfully for the treatment of PDPH.[7],[8] Case reports detailing successful prophylactic use of hydrocortisone following inadvertent dura puncture during epidural blocks suggest it may play a positive role in the prevention of PDPH.[9] The only previously published controlled trial that investigated the use of hydrocortisone for the prevention of PDPH, conducted by Mortazavi et al.,[10] found it to be ineffective. The authors of the study stated that their study was under-powered, having only eighty participants. As such, the need remained for a better powered study like this one.

This study investigated the efficacy of a single dose of IV hydrocortisone 100 mg in preventing PDPH following spinal anesthesia for cesarean section. Its effect on intensity and duration of PDPH in those who eventually developed such, as well as intraoperative and postoperative side effects attributable to hydrocortisone were also evaluated.


  Subjects and Methods Top


This double-blind randomized controlled study was conducted after institutional ethical approval was obtained and in accordance with the Helsinki Declaration. A written informed consent was obtained from all participants. A total of 400 parturients scheduled for elective cesarean section under spinal anesthesia were recruited for the study between October 5, 2017, and July 22, 2018. The sample size for each group was calculated using the formula for comparison of two equal groups with binary outcome.[11] Using 22.7%[4] as the highest incidence of PDPH in a local study, assuming a 50% reduction in incidence of PDPH if intervention is effective and an attrition of 10%, the calculated sample size per group was 187. This was rounded up to 200 per group, making 400 patients for the two groups hydrocortisone group (Group H) and control group (Group C).

Inclusion criteria included the age of 18 years and above and an ASA physical status I or II. Exclusion criteria were unwillingness to consent, previous history of PDPH or history of chronic/recurrent headaches, history of allergy to hydrocortisone, peptic ulcer disease, diabetes mellitus, hypertensive disease of pregnancy or an active fungal, viral or bacterial infection. Patients were randomized using a computer-generated set of random numbers that were kept in sealed, consecutively numbered envelopes. Drug preparation was done by the theater pharmacist and handed over to the attending anesthetist who was not otherwise involved with the study.

Baseline vital signs and blood sugar level were obtained. All subarachnoid blocks (SAB) were performed in sitting position at L3/L4 interspace, by the same anesthetist (the lead investigator). Only 25G Quincke needles were used for SAB. Attempts at SAB were limited to no more than two dural punctures. Following a successful block, the lead investigator exited the suite while the attending anesthetist continued with the conduct of anesthesia. On delivery of the baby, patients in Group H were given IV hydrocortisone 100 mg diluted to 2 ml while those in Group C received 2 ml of 0.9% saline. Immediately after surgery, blood sugar level was checked, and then again at 8 h after surgery using the same glucometer (Accu-Chek Active, by Roche).

The presence of a frontal and/or occipital headache, worsened by sitting or standing and relieved by lying supine, occurring within 5 days of spinal anesthesia, was deemed diagnostic of PDPH. Patients were assessed for PDPH 6 hourly for the first 48 h (excluding patients' sleeping hours), then 12 hourly until hospital discharge. Following discharge, follow-up occurred daily by telephone call until 5 days postsurgery or until headache resolved in those who developed PDPH. The 11-point numerical rating scale (NRS) was used to assess severity of headache. Grading of headache severity was into mild (NRS score of 1–3), moderate (4–6), or severe (7–10). Patients who developed PDPH were treated conservatively with bed rest in supine position, adequate hydration with a minimum daily fluid intake of 3 L and continued simple analgesic (paracetamol 1 g 8 hourly). Oral diclofenac 50 mg 12 hourly was added to the treatment of patients having moderate-to-severe PDPH not responding to conservative care. An epidural blood patch (EBP) was offered to patients with persistently severe headache (NRS score of 7 and above, lasting more than 2 days) in spite of conservative management.

Other postoperative complications specifically checked for include persistent dyspepsia, operation site infection evidenced by pus discharge or wound breakdown, and persistent vomiting (>2 episodes per day or vomiting on 2 consecutive days).[12]

The primary outcome measure was incidence of PDPH. Secondary outcome measures included maximum NRS score, need for further treatment of PDPH with diclofenac or EBP, duration of PDPH and perioperative side effect(s) of hydrocortisone.

Data obtained were entered into and analyzed using IBM Statistical Package for Scientific Solutions (SPSS) version 20 software (IBM (International Business Machines Corporation), Armonk, New York, USA). Qualitative variables are presented in tables and charts as frequencies and percentages while quantitative data are presented as mean and standard deviation as appropriate. Comparisons of means between the two groups were done using the independent Student's t-test. Paired t-test was utilized to compare means of blood sugar levels from baseline to immediate postsurgery and from immediate postsurgery to 8 h postsurgery, respectively. A P < 0.05 was considered statistically significant.


  Results Top


A total of 452 patients scheduled for elective cesarean section under spinal anesthesia were assessed for eligibility for this study, out of which 400 patients were randomized into the two study groups [Figure 1]. Three hundred and ninety-one patients completed the study and were included for analysis; 197 in Group H and 194 in Group C. The demographic characteristics and procedural/clinical variables of the two groups were similar as shown in [Table 1].
Figure 1: Study consort flow diagram

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Table 1: Demographic characteristics and clinical variables

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Of the 391 parturients that completed the study, 94 patients met the criteria for PDPH amounting to a total incidence of 24.0%. In Group H, 46 patients (23.4%) developed PDPH while 48 patients (24.7%) had PDPH in Group C; P = 0.813 (Chi-square) [Table 2]. Mean PDPH onset time in Group H was 47.85 ± 19.53 h compared to 53.58 ± 20.91 h in Group C; P = 0.173 (Student's t-test). Maximum NRS score ranged from 2 to 10 in both groups with mean values of 6.20 ± 1.80 in Group H and 6.23 ± 1.87 in Group C; P = 0.930 (Student's t-test). Majority of the parturients with PDPH had moderate-to-severe headache intensities in both groups [Figure 2].
Table 2: Incidence of postdural puncture headache in both groups

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Figure 2: Distribution of postdural puncture headache severity levels using numerical rating score grading

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Postural headache was the sole presentation in 43.6% of patients with PDPH. The most common symptoms associated with postural headache were neck stiffness (44.7%) and dizziness (14.9%), which occurred in statistically similar proportions between both groups [Table 3]. About half (48.9%) of the parturients with PDPH had complete resolution of headache within 2 days and no patient had PDPH lasting beyond 6 days in both groups. The mean duration of PDPH in Group H was 2.87 ± 1.44 days and 2.73 ± 1.38 days in Group C; P = 0.630 (Student's t-test).
Table 3: Frequency of associated symptoms in patients with postdural puncture headache

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All patients who developed PDPH were treated conservatively with bed rest, hydration, and paracetamol. Oral diclofenac was added to the treatment for PDPH of 28 patients (60.9%) in Group H compared to 26 patients (54.2%) in Group C; P = 0.538 (Chi-square). No patient received an EBP for management of PDPH in this study. However, three patients (1 in Group H and 2 in Group C) were offered EBP as part of their management plan but declined.

Baseline vital signs were similar between the two groups. Hypotension (a >20% reduction in baseline systolic blood pressure) was the most common intraoperative complication occurring in 72 parturients (36.5%) in Group H and 75 parturients (38.7%) in Group C; P = 0.678 (Chi-square) [Table 4]. Other intraoperative complications documented showed no statistically significant difference between both groups.
Table 4: Incidence of intraoperative complications in both groups

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The mean baseline and immediate postoperative blood sugar levels were comparable between both groups with P = 0.84 and 0.336, respectively (Student's t-test) [Table 5]. Mean blood sugar levels at 8 h after surgery showed a significantly higher value for Group H with 97.60 ± 23.81 mg/dl, compared to Group C with 82.07 ± 21.11 mg/dl; P = 0.000 (Student's t-test). Within Group H, there was a significant increase in blood sugar levels from baseline to immediate postsurgery (P = 0.003), as well as from immediate postsurgery to 8 h after surgery (P = 0.000; Paired t-test) [Table 5]. Within Group C, a significant increase was observed from baseline sugar level to immediate postoperative sugar level (P = 0.000; Paired t-test) while no significant change in blood sugar levels occurred from immediate postsurgery to 8 h postsurgery.
Table 5: Intra and intergroup comparison of mean blood sugar levels

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In the postoperative period, persistent vomiting occurred in three patients; one patient (0.5%) in Group H and two patients (1.0%) in Group C; P = 0.621 (Chi-square). No other postoperative complications attributable to hydrocortisone were recorded.


  Discussion Top


This study found that IV hydrocortisone 100 mg given prophylactically was not better than placebo in reducing the incidence of PDPH among parturients who had spinal anesthesia for cesarean delivery. Likewise, IV hydrocortisone 100 mg did not reduce headache intensity among parturients who suffered PDPH as the mean maximum NRS score as well as the distribution of NRS-graded severity were similar between both groups (P = 0.930 and P = 0.714, respectively).

The findings of this study are similar to the observations of Mortazavi et al.,[10] following use of IV hydrocortisone as prophylaxis for PDPH following SAB. They found that prophylactic IV hydrocortisone 100 mg had no significant effect on the prevalence of PDPH when compared with placebo at 12 h (P = 0.633), 24 h (P = 0.579), 48 h (P = 0.576), and 7 days (P = 0.502) after SAB. It similarly had no effect on headache intensity among those who developed PDPH at the same time intervals (P = 0.231, 0.344, 0.351, and 0.302, respectively). The average time from SAB to administration of IV hydrocortisone was 18.73 ± 7.02 min in this study. This delay in drug administration does not appear to have had any impact on the outcome of the study since Mortazavi et al.,[10] administered IV hydrocortisone 15 min prior to SAB and still found no significant difference in PDPH prevalence and headache intensity.

The successful use of hydrocortisone for the treatment of PDPH has been attributed largely to both salt and water retention (a mineralocorticoid effect) and anti-inflammatory effects that cause suppression of release of pro-inflammatory mediators of pain at the dura puncture site (a glucocorticoid effect).[7],[13] However, following dura puncture, an inflammatory response is required to produce the fibroblastic proliferation that leads to closure of the dural opening. It is possible that the glucocorticoid anti-inflammatory effect exerted by prophylactically administered hydrocortisone in this study also delayed closure of the dura opening leading to prolonged CSF leakage. The short duration of action of hydrocortisone, averaging 8–12 h, means that this possible unwanted effect is not sustained. Conversely, any possible beneficial effect from its mineralocorticoid actions is similarly not sustained following a single dose. Perhaps, repeated doses as utilized by Neves et al.,[9] in their case reports may prove more effective for the prevention of PDPH.

Hydrocortisone as used in this study did not cause an increase in the incidence and severity of PDPH. Another steroid, dexamethasone, has been associated with a higher incidence and increased severity of PDPH when given prophylactically.[14] This difference in effects between the 2 steroids may be due to differences in their pharmacodynamics. Dexamethasone has 25 times the glucocorticoid potency of hydrocortisone, zero mineralocorticoid effect and a longer duration of action ranging between 36 and 72 h.[15] A more intense anti-inflammatory effect, coupled with its longer duration of action, probably leads to a sustained leakage of CSF that results in an increased incidence and severity of PDPH with dexamethasone use.

Lack of mineralocorticoid activity in dexamethasone also means that any possible beneficial effects from fluid retention vis-a-vis increased CSF production and functional dural closure from dura edema are nonexistent. It is possible that these beneficial mineralocorticoid effects present with hydrocortisone use offset its unwanted glucocorticoid actions, thereby preventing an increase in PDPH incidence and headache severity as observed in this study.

Apart from headache intensity, other clinically important indicators of PDPH severity include number and severity of associated symptoms as well as the duration of headache. Prophylactically, administered IV hydrocortisone 100 mg had no significant effect on these parameters. Since IV hydrocortisone did not reduce the incidence and severity of PDPH, it is not surprising that there was no significant difference, between the two groups, in the need for further treatment of headache beyond the conventional bed rest, hydration, and paracetamol. Although three parturients (1 in the hydrocortisone group and 2 in the saline group) qualified to have an EBP in this study, they all declined to have it. The reasons given for declining EBP are unwillingness to have an invasive treatment and avoidance of the attendant risk of an inadvertent dural puncture.

Hypotension and bradycardia are well recognized complications of SAB. Most of the observed cases of hypotension and bradycardia started within the first 15 min after SAB, often prior to the administration of the study drug. There was no statistically significant difference in the occurrence of either complication between both groups. As such, IV hydrocortisone 100 mg had no adverse hemodynamic effect in this study. More patients in Group H had intraoperative dyspepsia (3.6%) as well as nausea and/or vomiting (9.6%) compared to Group C (1.5% and 5.7%, respectively). While these are known complications associated with hydrocortisone use, the observed increase in their incidences were not statistically significant.

Shivering occurred in a lower percentage of parturients in the hydrocortisone group compared to the saline group but this difference was not statistically significant (12.7% vs. 16.5%; P = 0.317). This is in contrast to the findings of Safavi et al.,[16] where IV hydrocortisone administered as single doses of 1 mg/kg and 2 mg/kg significantly reduced the incidence of perioperative shivering following spinal anesthesia, compared to placebo (P = 0.039 and P = 0.0001, respectively). This difference in effect on perioperative shivering may be due to the delay in the administration of IV hydrocortisone in this study. Since orthopedic, and not obstetric, patients were recruited for the study by Safavi et al.,[16] the respective doses of IV hydrocortisone were administered 10 min prior to SAB. Allowing for delivery of the baby(ies) brought about a delay in hydrocortisone administration in this study. In some patients, shivering already occurred before drug administration, thereby masking any possible prophylactic benefit from hydrocortisone use.

This study also demonstrated that IV hydrocortisone caused a statistically significant rise in blood sugar level postoperatively following a single dose. Cesarean section, like other forms of surgery, induces a neuroendocrine response characterized by increased serum levels of catabolic hormones such as cortisol, glucagon, epinephrine, norepinephrine, growth hormone, and thyroid hormones, but diminished secretion of insulin.[17] The initial significant rise in mean blood sugar levels observed within both groups from baseline to immediate postsurgery is likely the effect of the stress response to surgery.

While no further increase in blood sugar levels was observed at 8 h postsurgery in the control group, a larger and statistically significant increase was observed in the hydrocortisone group, in keeping with the well-established hyperglycemic attribute of hydrocortisone. This hyperglycemic effect readily reverses once the duration of action of the steroid elapses, unless when repeated doses are administered.[18] Since a single dose of hydrocortisone was utilized in this study, it is unlikely that the observed hyperglycemic effect would have been sustained much beyond 12 h (the upper limit of hydrocortisone's duration of action). However, no further blood sugar checks were conducted beyond 8 h after surgery for this study.

One patient in the hydrocortisone group and two patients in the control group had persistent vomiting (P = 0.621). No other postoperative complication attributable to hydrocortisone was recorded. Thus, the only significant perioperative side effect of a single dose of IV hydrocortisone 100 mg observed in this study was an increase in mean blood sugar level at 8 h postsurgery. Nonetheless, the recorded mean blood sugar level of 97.60 mg/dl is well within the normal range for a random blood sugar.

Limitations of this study include the use of a single dose of hydrocortisone for all patients irrespective of weight. While this approach ensured simplicity of dosing, it may have amounted to under-dosing for some patients. The presence of a postural headache was also made mandatory for the diagnosis of PDPH in this study though the diagnostic criteria for PDPH recognizes that a postural component is usually, but not always present.[19]


  Conclusions Top


Prophylactic IV hydrocortisone 100 mg does not reduce the incidence or severity of PDPH following spinal anesthesia for cesarean section.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Basurto Ona X, Uriona Tuma SM, Martínez García L, Solà I, Bonfill Cosp X. Drug therapy for preventing post-dural puncture headache. Cochrane Database Syst Rev 2013;(2):CD001792.  Back to cited text no. 5
    
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Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol 2001;33:289-94.  Back to cited text no. 6
    
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Neves JF, Vieira VL, Saldanha RM, Vieira Fde A, Coutinho Neto M, Magalhães MG, et al. Hydrocortisone treatment and prevent post-dural puncture headache: Case reports. Rev Bras Anestesiol 2005;55:343-9.  Back to cited text no. 9
    
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Mortazavi MT, Kazaj MA, Movassaghi R. Prophylactic effects of hydrocortisone on post dural puncture headache after spinal anesthesia. Arch Anesthesiol Crit Care 2018;4:426-9.  Back to cited text no. 10
    
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Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture. Anesthesiology 2010;113:413-20.  Back to cited text no. 13
    
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Yousefshahi F, Dahmardeh AR, Khajavi M, Najafi A, Khashayar P, Barkhordari K. Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: A double-blind randomized clinical trial. Acta Neurol Belg 2012;112:345-50.  Back to cited text no. 14
    
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Gupta P, Bhatia V. Corticosteroid physiology and principles of therapy. Indian J Pediatr 2008;75:1039-44.  Back to cited text no. 15
    
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Safavi M, Honarmand A, Khosravi F, Sariazdi H, Nazem M. The evaluation of effects two different doses of hydrocortisone on the intensity of perioperative shivering in elective surgery under spinal anesthesia: A double-blind randomized controlled trial study. J Res Med Sci 2016;21:40.  Back to cited text no. 16
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Desborough JP. The stress response to trauma and surgery. Br J Anaesth 2000;85:109-17.  Back to cited text no. 17
    
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Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, González-González JG, Tamez-Peña AL. Steroid hyperglycemia:Prevalence, early detection and therapeutic recommendations: A narrative review. World J Diabetes 2015;6:1073-81.  Back to cited text no. 18
    
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