clinical study the efficacy of intranasal desmopressin as an ...department of emergency medicine,...

Clinical StudyThe Efficacy of Intranasal Desmopressin as an Adjuvant in theAcute Renal Colic Pain Management

Kambiz Masoumi1 Ali Asgari Darian1 Arash Forouzan1 Hassan Barzegari1

Fakher Rahim2 Maryam Feli1 Mehdi Fallah Bagher Sheidaii1 and Samaneh Porozan1

1Department of Emergency Medicine Imam Khomeini General Hospital Ahvaz Jundishapur University of Medical SciencesAzadegan Avenue Ahvaz Khuzestan Province 6193673166 Iran2Toxicology Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz 6193673166 Iran

Correspondence should be addressed to Arash Forouzan md 89864yahoocom

Received 29 July 2014 Revised 23 November 2014 Accepted 24 November 2014 Published 8 December 2014

Academic Editor Anna Maria Aloisi

Copyright copy 2014 Kambiz Masoumi et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

The aim of this study was to compare analgesic effect of intramuscular (IM) sodium diclofenac and intranasal desmopressincombination with IM sodium diclofenac alone in patients with acute renal colic In this randomized double-blind clinical trial allpatients aged 18 to 55 years who were diagnosed as acute renal colic and met the inclusion and exclusion criteria were randomizedinto two groups to receive 40 120583g intranasal desmopressin spray and 75mg IM sodium diclofenac combination (Group A) or75mg IM sodiumdiclofenac alone (GroupB)Thepain score of patients was assessed using a visual analogue scale (VAS) at baseline15 30 45 and 60 minutes after administration Of all 159 patients who were assessed for eligibility finally the results of 120 patientswere analyzed There was no significant difference regarding age and gender between two groups The baseline VAS score wasnot significantly different between two groups (119875 = 044) The Mean plusmn SD scores of two groups reduced 15 minutes after drugadministration but this decrease was significantly more in Group A compared with Group B (119875 = 002) This pattern continuedin minutes 30 45 and 60 of drug administration Our results showed that desmopressin could be used as an effective adjuvant inacute renal colic pain management

1 Introduction

Pain is the most common presenting complaint in patientswho present to the Emergency Department which presentsin 50ndash75 of all the patients [1] Renal colic pain is probablythe worst excruciatingly painful event a person can endureAnnually approximately 12million people are suffering fromrenal colic which accounts for about 1 of all hospital admis-sions [2]Thepain generated by renal colic is primarily causedby the dilation stretching and spasm caused by the acuteureteral obstruction The pattern of the pain depends on theindividualrsquos pain threshold and perception and on the speedand degree of the changes in hydrostatic pressure within theproximal ureter and renal pelvis whichwas related to positionof the stone within urinary tract Severity of pain is related tothe degree and site of obstruction presence of ureteral spasmand presence of any associated infection not to the size of

the stones Injectable narcotic analgesics are choice of themedical therapy in patients with acute renal colic Althoughopioids are cheap and effective in pain management they areaddictive and cause different side effects like nausea vomit-ing drowsiness and impaired consciousness [2] In additionnonsteroidal anti-inflammatory drugs (NSAIDs) were effec-tive in treating the pain of renal colic for ages The mostfrequent drug which is used is injectable sodium diclo-fenac Its peak plasma concentration is 10ndash22 minutes afteradministration [3]

The need for finding the best drug for renal colic painmanagement is still crucial It has been suggested thatdecrease in diuresis by antidiuretic hormone helps to relievethe pain of renal colic immediately [4ndash6] Desmopressin (1-desamino-8-d-arginine vasopressin) is a synthetic structuralanalog of the antidiuretic hormone which has strongerantidiuretic effects and is longer lasting and less vasopressor

Hindawi Publishing CorporationPain Research and TreatmentVolume 2014 Article ID 320327 5 pageshttpdxdoiorg1011552014320327

2 Pain Research and Treatment

[7ndash9] The mechanism by which desmopressin relieves renalcolic pain has not been fully determined but probably ismanifold [7] Desmopressin has been used for renal colic painmanagement previously but its effectiveness as an adjuvant toopioids or NSAIDs should be evaluated more

This studywas conducted to compare the analgesic effectsof intramuscular sodium diclofenac and intranasal desmo-pressin combination with intramuscular sodium diclofenacalone in patients with acute renal colic

2 Materials and Methods

This randomized double-blind clinical trial was carried outin the Emergency Department (ED) of Imam KhomeiniHospital Ahvaz Iran from April 2014 to July 2014 Allpatients complaining of renal colic aged between 18 and 55years presenting to the ED were assessed for the eligibility ofthe study

The diagnosis of renal colic was made based on chiefcompliant (flank pain) history andphysical examination andpositive history of renal stone The presence of renal stonewas confirmed in all patients using ultrasound or computedtomography

Patients with hypertension coronary artery diseaserhinitis influenza coagulopathy anticoagulant therapy pep-tic ulcer disease asthma kidney failure liver failure preg-nancy use of analgesics within 4 hours and Alpha blockersbefore admission history of addiction surgery on the kidneyor ureter and fluids therapy immediately before admissionwere excluded During the study if a patient could not bearthe pain and did not want to continue heshe was excluded

Eligible patientswere randomized between two groups (Aand B) in a 1 1 ratio using a computer-generated code Theidentities of the study drugs were recorded in a documentfolded four times and then covered for allocation conceal-ment When a patient was enrolled in the trial a study nurseretrieved one of the drugs from a box The medication wasprepared by the study nurse and administered by the secondnursewhowas blinded to the purpose of the interventionThestudy drugs were identical in color and appearance thereforethe patients and study physicians were blinded to identity

First using 10-centimeter visual analog scale (VAS) allparticipants were assessed for severity of pain (10 = the worstpossible level of pain and 1 = painless) For this purpose theemergency physician showed the printed VAS ruler to thepatients and asked them to show the number that representstheir perception of their current painThen inGroupA 40120583gof intranasal desmopressin spray (Minirin Ferring KielGermany 500 120583gvial 10 120583gpuff) equal to 4 puffs of availableproducts (each puff contains 10 micrograms into a nostrilalternately) combined with 75mg intramuscular sodiumdiclofenac (Osveh Pharma Co Tehran Iran 75mg2cc) wasadministered Group B received 75mg intramuscular sodiumdiclofenac (Osveh Pharma Co Tehran Iran 75mg2cc) andNACL 065 (DECOSALIN 065 Raha Company Iran20mL nasal spray) intranasal spray (4 puffs each puff intoa nostril alternately)

All participants in both groups were assessed for severityof pain according to VAS standards 15 30 45 and 60minutes

Table 1 Comparing age and gender distribution of patients betweentwo groups (A and B)

Variable Group A (60) Group B (60)Age (Mean plusmn SD) years 329 plusmn 824 363 plusmn 989Age (number ())le35 27 (45) 32 (534)36ndash45 19 (316) 22 (366)46ndash55 14 (234) 6 (10)

Gender (number ())Female 14 (234) 15 (25)Male 46 (766) 45 (75)

after drug administration and differences in pain level of2 or more VAS units were considered significant After 30minutes if severity of pain was equal to or more than 5 VASunits 5mg morphine sulfate was administered intravenouslyto the patient as rescue therapy If any degree of pain persistedafter minute 60 an additional dose of morphine sulfate wasadministered

Before commencement of the study we obtained the codeof ethics numbered ETH-359 from the Ethical Committeeof Ahvaz Jundishapur University of Medical Sciences andevery stage of the study was in accordance with the HelsinkiDeclaration 1975 Written consent was obtained from all par-ticipating patients and confidentiality of patientrsquos personaldetails was maintained This study was registered at IranrsquosClinical Trials Registration Centre and the relevant code wasobtained

Statistical Analysis To consider 120572 = 005 120573 = 02 power =80 and the final differences between the two groups atleast 2 scores on VAS the sample size was calculated at least40 in each group Continuous variables were summarized asMean plusmn SD and categorical variables as ratios Two-tailedindependent 119905-test was carried out to compare quantitativevariables with normal distribution and chi-square was donefor comparing qualitative ones

3 Results

Initially 159 potential study candidates were assessed foreligibility however 36 subjects did not meet the inclusionand exclusion criteria Three participants refused to finishthe study Eventually 120 (60 in each group) patients wereallocated randomly between the two groups and data fromthese participants were analyzed

Baseline characteristics of two groups participants arepresented in Table 1

There was no significant difference regarding baselineVAS pain score (Mean plusmn SD) between two groups (928 plusmn 047versus 935 plusmn 035 119875 value = 044)

The Mean plusmn SD scores of two groups reduced 15 minutesafter drug administration but this decrease was significantlymore in Group A compared with Group B (119875 = 002) Thispattern continued in minute 30 minute 45 and minute 60 ofdrug administration (Table 2 Figure 1)

Pain Research and Treatment 3

Table 2 Comparing VAS pain score (Mean plusmn SD) between twogroup participants across the time (15 30 45 and 60 minutes) afterdrug administration

Group A Group B 119875 valuePain score (151015840) 543 plusmn 270 651 plusmn 246 002Pain score (301015840) 452 plusmn 261 568 plusmn 278 002Pain score (451015840) 364 plusmn 236 453 plusmn 215 003Pain score (601015840) 242 plusmn 194 328 plusmn 243 003

2

3

4

5

6

7

8

9

10

Minute 0

Group AGroup B

Minute 15 Minute 30 Minute 45 Minute 60

Figure 1 Comparing the pattern of pain score decrease across thetime between Group A and Group B patients

However the physician was supposed to administer 5mgmorphine sulfate in 23 and 27 patients in GroupA andGroupB respectively in minute 30 because their pain score washigher than 5 Also finally 11 patients in Group A and 19patients inGroupB received 5mgmorphine sulfate regardingany degree of pain at minute 60 No side effects were detectedin either group

Findings of ultrasound or CT scanning in two groupsshowed one to three stones measured 3mm to 11mm inurinary tract system from calyces to bladder in which atleast one stone has been localized between ureteropelvic andureterovesical junction and exceptionally two patients withonly one calyceal stone in Group A

4 Discussion

Desmopressin is the first line of replacement therapy inthe nocturnal enuresis and central diabetes insipidus [7ndash9] Likely the antidiuretic mechanism of desmopressin isresponsible for making it effective for the treatment ofrenal colic [7 10] Desmopressin suppresses spontaneouscontractions of circular smooth muscle fibers in the renalpelvis of rabbits [11] Some researchers have reported the roleof desmopressin in stimulating the release of beta-endorphinsby the hypothalamus which could prove its effective centralanalgesic [12] Central mechanism for inducing analgesia can

also be an acceptable hypothesis However effects of desmo-pressin on final passage of stones are unknown Intranasalform of the drug (500 120583g5mL and 10 120583gpuff) is availablewhich is administered into a nostril The biphasic half-livesof intranasal desmopressin were 78 and 755 minutes for thefast and slow phases respectively Usually only a single doseof 40120583g4 puffs of intranasal desmopressinmay be prescribed[3]

Our results showed that the combination of nasal desmo-pressin and IM diclofenac is more effective than IM diclo-fenac alone in acute renal colic pain reductionThis differencestarted 15 minutes after drug administration and was main-tained during 60 minutes of follow-up

The pain generated by renal colic is primarily causedby the dilation stretching and spasm caused by the acuteureteral obstruction In the ureter an increase in proximalperistalsis through activation of intrinsic ureteral pacemakersmay contribute to the perception of pain Muscle spasmincreased proximal peristalsis local inflammation irritationand edema at the site of obstruction may contribute tothe development of pain through chemoreceptor activationand stretching of submucosal free nerve endings Mentionedmechanisms (antidiuretic effects suppression of spontaneouscontractions of circular smooth muscle fibers in the urinarytract system and stimulating the release of beta-endorphinsby the hypothalamus) were considered reasonable causes foreffective role of desmopressin in our study

In 1994 El-Sherif et al [4] investigated the effectivenessof desmopressin in 18 patients with acute renal colic painmanagement in 30 minutes Eight patients had completepain relief 30 minutes after intranasal desmopressin sprayadministration Nine patients need IM diclofenac Theirresults are in line with ours although the small sample sizeshort follow-up duration and lack of control group make thejudgment difficult

Constantinides et al 1998 evaluated desmopressin effi-cacy in 108 renal colic patients Over fifty-three percentof their patients respond after 30 minutes Others receivedprostaglandin synthesis inhibitors or pethidine for pain reliefThey concluded that desmopressin could be used for renalcolic pain management [13]

Lopes et al 2001 compared the efficacy of nasal desmo-pressin spray with IM diclofenac in three different groups(first second and third group received desmopressindiclofenac and desmopressin-diclofenac combination resp)Their results revealed that pain score reduction was equalin all groups 10 and 20 minutes after drug administrationbut at minute 30 there was a slight increase in pain scorein the first group They did not follow patients after minute30 but in our study pain reduction decreased significantlyin desmopressin-diclofenac combination group since 15min-utes after administration and during one-hour follow-up thisdifference was maintained [14]

In 2010 Kheirollahi et al [15] in a clinical trial studied114 patients who randomly were allocated in two groupsincluding first group which received 20mg intramuscularhyoscine N-butyl bromide at admission time and secondgroup which received 20120583g of intranasal desmopressin incombination with 20mg intramuscular hyoscine N-butyl


bromide In the first group the mean of pain level showeda decrease after 30 minutes but further decreasing did notoccur however in the second group the pain consistentlydecreased and the mean after 60 minutes was significantlydecreased In another study Roshani et al [3] in a double-blind controlled clinical trial determined the effect of thecombination of intranasal desmopressin spray and diclofenacsodium suppository in 50 patients with acute renal colicand compared it with diclofenac sodium suppository alonePatients in the first group received intranasal desmopressin40 120583g plus diclofenac sodium suppository 100mg andpatients in the second group received diclofenac sodiumsuppository 100mg plus a placebo spray consisting of normalsaline 09 They showed that intranasal desmopressin plusdiclofenac sodium suppository caused prompt pain reliefwith significant decreases in pain scores after 15 and 30minutes and suggested that intranasal desmopressin spray isa useful supplemental therapy for renal colic in combinationwith NSAIDs especially to reduce the use of opioids In 2012Moosavi Beladi et al [2] evaluated 70 patients with acuterenal colic that their results showed that desmopressin nasalspray is effective in rapid pain relief for acute renal colic sig-nificantly meanwhile synergistic effect of desmopressin anddiclofenac together can cause much better pain decreasingand less using of morphine

On the other hand Kumar et al [16] reported that intran-asal desmopressin is not an effective analgesic in renal colicand does not potentiate the effect of diclofenac Howeverslow phase of desmopressin action should be considered

Although several studies have evaluated the desmo-pressin efficacy in renal colic pain management there is adisagreement in their results

Desmopressin has several advantages such as ease ofadministration simplicity of delivery apparent lack of sideeffects and rapid action which makes it suitable for ambula-tory use It seems that desmopressin is a promising alternativeor adjunct to analgesics in patients with acute renal colicespecially in cases that there is contraindication for narcoticsor resistant pain to the standard medical therapy Besidesits biphasic half-life is a considerable advantage Not onlydoes it have rapid onset effect but also these analgesic effectsmaintain for a long duration

5 Conclusions

Our results showed that desmopressin could be used as aneffective adjuvant in acute renal colic pain management

Limitations

In this study we did not evaluate the desmopressin analgesiceffect in a separate group Our study has been designed forabout 60 minutes and we did not record more informationof patients conditions Also we did not evaluate intranasaldesmopressin effect regarding its slow phase of half-life (755minutes) These problems associated with individualrsquos painthreshold and perception were considered limitation of ourstudy

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

This study was Dr Mehdi Fallah Bagher Sheidaiirsquos postgradu-ate thesis which is recordedwith noD461 andwas supportedby a grant from Ahvaz Jundishapur University of MedicalSciences

References

[1] P Tanabe and M Buschmann ldquoA prospective study of ED painmanagement practices and the patientrsquos perspectiverdquo Journal ofEmergency Nursing vol 25 no 3 pp 171ndash177 1999

[2] S S Moosavi Beladi A Asgari Darian A Forouzan HKalantar and KMasoumi ldquoRenal colic pain relief by intranasaldesmopressinrdquo Life Science Journal vol 9 no 4 pp 3354ndash33582012

[3] A Roshani S Falahatkar I Khosropanah et al ldquoAssessment ofclinical efficacy of intranasal desmopressin spray and diclofenacsodium suppository in treatment of renal colic versus diclofenacsodium alonerdquo Urology vol 75 no 3 pp 540ndash542 2010

[4] A E El-Sherif M Salem H Yahia W A S Al-Sharkawyand M Al-Sayrafi ldquoTreatment of renal colic by desmopressinintranasal spray and diclofenac sodiumrdquoThe Journal of Urologyvol 153 no 5 pp 1395ndash1398 1995

[5] F Marumo and I S Edelman ldquoEffects of Ca++ and prostagl-andin E

1on vasopressin activation of renal adenyl cyclaserdquoThe

Journal of Clinical Investigation vol 50 no 8 pp 1613ndash16201971

[6] A Holdgate and T Pollock ldquoSystematic review of the relativeefficacy of non-steroidal anti-inflammatory drugs and opioidsin the treatment of acute renal colicrdquo British Medical Journalvol 328 no 7453 pp 1401ndash1404 2004

[7] S Naghizadeh A Kefi H S Dogan B Burgu B Akdoganand S Tekgul ldquoEffectiveness of oral desmopressin therapy inposterior urethral valve patients with polyuria and detection offactors affecting the therapyrdquo European Urology vol 48 no 5pp 819ndash825 2005

[8] A Triantafyllidis S Charalambous A G Papatsoris et alldquoManagement of nocturnal enuresis in Greek childrenrdquo Pedi-atric Nephrology vol 20 no 9 pp 1343ndash1345 2005

[9] A G Robinson ldquoDDAVP in the treatment of central diabetesinsipidusrdquo The New England Journal of Medicine vol 294 no10 pp 507ndash511 1976

[10] UMoro S de Stefani A Crisci P de Antoni C A Scott and CSelli ldquoEvaluation of the effects of desmopressin in acute ureteralobstructionrdquo Urologia Internationalis vol 62 no 1 pp 8ndash111999

[11] Y Kimoto and C E Constantinou ldquoEffects of [1-desamino-8-D-arginine]vasopressin and papaverine on rabbit renal pelvisrdquoEuropean Journal of Pharmacology vol 175 no 3 pp 359ndash3621990

[12] R L Kohl ldquoBeta-endorphin and arginine vasopressin followingstressful sensory stimuli in manrdquo Aviation Space and Environ-mental Medicine vol 63 no 11 pp 986ndash993 1992

[13] C Constantinides V Kapralos TManousakas DMitropoulosC Alamanis and C Dimopoulos ldquoManagement of renal colic


with intranasal desmopressin sprayrdquoActa Urologica Belgica vol66 no 4 pp 1ndash3 1998

[14] T Lopes J S Dias J Marcelino J Varela and S Ribeiro ldquoAnassessment of the clinical efficacy of intranasal desmopressinspray in the treatment of renal colicrdquo BJU International vol 87no 4 pp 322ndash325 2001

[15] A-R Kheirollahi M Tehrani and M Bashashati ldquoA compari-son of the effect of intranasal desmopressin and intramuscularhyoscine N-butyl bromide combination with intramuscularhyoscine N-butyl bromide alone in acute renal colicrdquo Journalof Research in Medical Sciences vol 15 no 4 2010

[16] S Kumar N C Behera D Sarkar S Prasad A K Mandal andS K Singh ldquoA comparative assessment of the clinical efficacy ofintranasal desmopressin spray and diclofenac in the treatmentof renal colicrdquo Urological Research vol 39 no 5 pp 397ndash4002011

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Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


[7ndash9] The mechanism by which desmopressin relieves renalcolic pain has not been fully determined but probably ismanifold [7] Desmopressin has been used for renal colic painmanagement previously but its effectiveness as an adjuvant toopioids or NSAIDs should be evaluated more

This studywas conducted to compare the analgesic effectsof intramuscular sodium diclofenac and intranasal desmo-pressin combination with intramuscular sodium diclofenacalone in patients with acute renal colic

2 Materials and Methods

This randomized double-blind clinical trial was carried outin the Emergency Department (ED) of Imam KhomeiniHospital Ahvaz Iran from April 2014 to July 2014 Allpatients complaining of renal colic aged between 18 and 55years presenting to the ED were assessed for the eligibility ofthe study

The diagnosis of renal colic was made based on chiefcompliant (flank pain) history andphysical examination andpositive history of renal stone The presence of renal stonewas confirmed in all patients using ultrasound or computedtomography

Patients with hypertension coronary artery diseaserhinitis influenza coagulopathy anticoagulant therapy pep-tic ulcer disease asthma kidney failure liver failure preg-nancy use of analgesics within 4 hours and Alpha blockersbefore admission history of addiction surgery on the kidneyor ureter and fluids therapy immediately before admissionwere excluded During the study if a patient could not bearthe pain and did not want to continue heshe was excluded

Eligible patientswere randomized between two groups (Aand B) in a 1 1 ratio using a computer-generated code Theidentities of the study drugs were recorded in a documentfolded four times and then covered for allocation conceal-ment When a patient was enrolled in the trial a study nurseretrieved one of the drugs from a box The medication wasprepared by the study nurse and administered by the secondnursewhowas blinded to the purpose of the interventionThestudy drugs were identical in color and appearance thereforethe patients and study physicians were blinded to identity

First using 10-centimeter visual analog scale (VAS) allparticipants were assessed for severity of pain (10 = the worstpossible level of pain and 1 = painless) For this purpose theemergency physician showed the printed VAS ruler to thepatients and asked them to show the number that representstheir perception of their current painThen inGroupA 40120583gof intranasal desmopressin spray (Minirin Ferring KielGermany 500 120583gvial 10 120583gpuff) equal to 4 puffs of availableproducts (each puff contains 10 micrograms into a nostrilalternately) combined with 75mg intramuscular sodiumdiclofenac (Osveh Pharma Co Tehran Iran 75mg2cc) wasadministered Group B received 75mg intramuscular sodiumdiclofenac (Osveh Pharma Co Tehran Iran 75mg2cc) andNACL 065 (DECOSALIN 065 Raha Company Iran20mL nasal spray) intranasal spray (4 puffs each puff intoa nostril alternately)

All participants in both groups were assessed for severityof pain according to VAS standards 15 30 45 and 60minutes

Table 1 Comparing age and gender distribution of patients betweentwo groups (A and B)

Variable Group A (60) Group B (60)Age (Mean plusmn SD) years 329 plusmn 824 363 plusmn 989Age (number ())le35 27 (45) 32 (534)36ndash45 19 (316) 22 (366)46ndash55 14 (234) 6 (10)

Gender (number ())Female 14 (234) 15 (25)Male 46 (766) 45 (75)

after drug administration and differences in pain level of2 or more VAS units were considered significant After 30minutes if severity of pain was equal to or more than 5 VASunits 5mg morphine sulfate was administered intravenouslyto the patient as rescue therapy If any degree of pain persistedafter minute 60 an additional dose of morphine sulfate wasadministered

Before commencement of the study we obtained the codeof ethics numbered ETH-359 from the Ethical Committeeof Ahvaz Jundishapur University of Medical Sciences andevery stage of the study was in accordance with the HelsinkiDeclaration 1975 Written consent was obtained from all par-ticipating patients and confidentiality of patientrsquos personaldetails was maintained This study was registered at IranrsquosClinical Trials Registration Centre and the relevant code wasobtained

Statistical Analysis To consider 120572 = 005 120573 = 02 power =80 and the final differences between the two groups atleast 2 scores on VAS the sample size was calculated at least40 in each group Continuous variables were summarized asMean plusmn SD and categorical variables as ratios Two-tailedindependent 119905-test was carried out to compare quantitativevariables with normal distribution and chi-square was donefor comparing qualitative ones

3 Results

Initially 159 potential study candidates were assessed foreligibility however 36 subjects did not meet the inclusionand exclusion criteria Three participants refused to finishthe study Eventually 120 (60 in each group) patients wereallocated randomly between the two groups and data fromthese participants were analyzed

Baseline characteristics of two groups participants arepresented in Table 1

There was no significant difference regarding baselineVAS pain score (Mean plusmn SD) between two groups (928 plusmn 047versus 935 plusmn 035 119875 value = 044)

The Mean plusmn SD scores of two groups reduced 15 minutesafter drug administration but this decrease was significantlymore in Group A compared with Group B (119875 = 002) Thispattern continued in minute 30 minute 45 and minute 60 ofdrug administration (Table 2 Figure 1)




2

3

4

5

6

7

8

9

10

Minute 0

Group AGroup B





4 Discussion














5 Conclusions


Limitations




Acknowledgment


References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















2

3

4

5

6

7

8

9

10

Minute 0

Group AGroup B





4 Discussion














5 Conclusions


Limitations




Acknowledgment


References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















5 Conclusions


Limitations




Acknowledgment


References


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















clinical study the efficacy of intranasal desmopressin as an ...department of emergency medicine,...

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