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Premedication With Single Dose of Acetazolamide for the Control ofReferral Shoulder Pain After Laparoscopic Cholecystectomy

Reza Movassaghi,1 Ali Peirovifar ,1 Davood Aghamohammadi,1,* Hassan Mohammadipour Anvari,1Samad EJGolzari, and !ohreh "ourehpaz1

Au#hor informa#ion $ Ar#i%le no#es $ &op'righ# and (i%ense informa#ion $

Abstract

Go #o)

1. ac!ground

The use of laparoscopic surgeries is escalating thanks to their advantages over the open surgeries.

In laparoscopic surgeries, the abdominal cavity is dilated using gases (usually CO2) for creating

essential space needed for instruments use. CO2 is a noninflammable gas, !hich dissolves in

blood rapidly and e"cretes from respiratory system (#).

$ostoperative pain has been a ma%or concern for physicians in both traditional and modern

medicine (2, &). 'everal symptomscomplications can be observed follo!ing laparoscopic

surgeries (&). $ostoperative pain is a ma%or concern in most surgeries (, *) including

cholecystectomy (+). umerous methods (, *) and medications from analgesics (-) to local

anesthetics () have been used to overcome postoperative pain. /ollo!ing laparoscopic surgery,

pain can be e"perienced in surgical area or radiated to the right shoulder. One of the proposed

mechanisms is insufflation of CO2 into the abdomen and its mi"ture !ith !ater and carbonic acid

and conse0uently irritation of surgical and subdiaphragmatic area. 1ue to common innervation,

pain can be sensed also in the right shoulder (, #3).

Insufflation of CO2 into the abdomen is almost painful and usually re0uires general anesthesia.

'ystemic absorption of CO2 from peritoneal layers causes hypercarbia (4tCO25 *3 mm6g),

!hich in turns impacts directly on cardiovascular system and indirectly on the hemodynamics

(increase in both the heart rate and arterial blood pressure) through stimulation of

sympathoadrenal a"is. $roduction of 67 ion in serous surfaces of abdominal organs during

CO2 insufflation into the abdominal cavity leads to p6 decline and pain stimulation conse0uently.

Insufflation of inert gases (e.g. helium, argon) instead of CO2 has advantages including avoiding

an increase in $aCO2 derived from absorption and its re0uired conse0uent hyperventilation. evertheless, this could be associated !ith undesirable conse0uences including but not limited to

decreased cardiac output and safety concerns in the event of gas embolism considering the lo!

blood solubility of the inert gases.

Insufflation of nitric o"ide instead of CO2 !ould be associated !ith less pain, !hich !ould

ultimately make laparoscopy possible to be performed !ith local anesthesia. 8eduction of

http://www.ncbi.nlm.nih.gov/pubmed/?term=Movassaghi%20R%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Movassaghi%20R%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Peirovifar%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Peirovifar%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Aghamohammadi%20D%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Aghamohammadi%20D%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Mohammadipour%20Anvari%20H%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=EJ%20Golzari%20S%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=EJ%20Golzari%20S%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Kourehpaz%20Z%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Kourehpaz%20Z%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Kourehpaz%20Z%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R3http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R3http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R6http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R7http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R8http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R9http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R10http://www.ncbi.nlm.nih.gov/pubmed/?term=Peirovifar%20A%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Aghamohammadi%20D%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Mohammadipour%20Anvari%20H%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=EJ%20Golzari%20S%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=EJ%20Golzari%20S%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pubmed/?term=Kourehpaz%20Z%5Bauth%5Dhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R3http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R3http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R6http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R4http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R5http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R7http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R8http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R9http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/#A29366R10http://www.ncbi.nlm.nih.gov/pubmed/?term=Movassaghi%20R%5Bauth%5D


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laparoscopy induced visceral pain is feasible and could be achieved !ithout anesthesia and along

!ith nitric o"ide insufflation by local anesthesia (+).

Carbonic anhydrase en9yme increases !ater and CO2 composition !hich in turn produces

carbonic acid. :ceta9olamide inhibits the en9yme, !hich seems to reduce postoperative

abdominal pain through preventing carbonic acid production (##). $revious studies reported

acidosis as one of the mechanisms for postoperative pain (#2). /urthermore, metabolic acidosis

is a kno!n complication of anhydrase carbonic en9yme (#&); it declines venous blood p6 and

the amount of 6CO& in plasma (#&, #). Considering $6 reduction of body fluids, aceta9olamide

does not prevent abdomen acidosis, even though intensifies acidosis; moreover, it contributes to

pneumoperitoneal pain (+).

The onset time of effects for aceta9olamide administered orally is about # #.* hours and the

duration of effect is #2 hours.


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diuretics, C' disorders, liver diseases, e"istence of any disorder in the right shoulder, previous

muscular diseases, and hypovolemia.

The intervention group (group I) received * mgkg oral aceta9olamide one hour before the

operation. The control group (group C) did not receive any medication. $remedication !as

performed by mida9olam 3.3* mgkg and fentanyl # @gkg before anesthesia induction.

Induction !as performed by propofol 2 mgkg and atracurium 3. mgkg. Intubation !as

performed after complete rela"ation and semisitting position !as maintained after!ards.

:nesthesia !as maintained !ith isoflurane and 2O. :fter the operation, pain severity !as

assessed on the shoulder and incision area by A:' at 3, 2, , +, , #3, #2, and 2 hours.

:dministration of analgesics !as recorded on considered hours. The 0uality of sleeping, nausea

and vomiting !ere also assessed.

: sample si9e analysis suggested that a total of +2 sub%ects are re0uired to detect a significant

difference bet!een the t!o groups !ith B 3.3* and 3= po!er in a t!osided test of the

hypothesis, but to consider possible lost to follo!up !e included -3 sub%ects.

1ata !as analy9ed using descriptive, T test, Chi s0uare test, and / test methods by '$'' version

.3 ('$'', Inc., Chicago ID, E'). 8epeated measure test !as used for evaluating pain severity in

various times. $ value less than 3.3* !as considered statistically significant. 1ata distribution

normality !as evaluated using FolmogorovG'mirnov test and HHplot. This study !as

registered in Iranian 8egistry of Clinical Trials as I8CT23#3-###--2#*.

Go #o)

(. Results

The mean age of sub%ects !as +.*+ years !ith mean of &.-# and &. years in I and C groups,

respectively. :mong patients, * sub%ects !ere female and ## males. $ain score mean before the

operation !as 3.& and 3.+& in I and C groups, respectively. In group C, & patients (.+=) had

bad 0uality of sleeping, 22 patients (+2.=) !ith medium 0uality of sleeping and #3 patients

(2.+=) !ith good 0uality of sleeping. In contrast, in the intervention group, 2 patients (*.-=)

had bad 0uality of sleeping, 2+ patients (-.&=) !ith medium 0uality of sleeping and - patients

(23=) !ith good 0uality of sleeping. :dministration of single dose of aceta9olamide had not any

statistically significant effect on sleep 0uality ($ #.333). /urthermore, there !as no statistically

significant difference bet!een the groups regarding nausea and vomiting on single dose

administration of aceta9olamide ($ #.333). 'houlder pain level in the intervention on 9ero hour

and control is demonstrated in Table #.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/table/tbl34119/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688810/table/tbl34119/


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Table #.

Shoulder Pain Level in the Intervention on Zero Hour and Controla

'ingle dose of aceta9olamide produced statistically significant reduction of shoulder pain at hour

9ero (immediately) after laparoscopy ($ 3.3#-). 6o!ever, there !as no statistically significant

difference regarding shoulder pain at hours 2, , +, , #3, #2, and 2 follo!ing laparoscopy.

/urthermore, single dose of :ceta9olamide !as not associated !ith any statistically significant

difference on the analgesic administration at hours 3, 2, , +, , #3, #2, and 2 follo!ing

laparoscopy.

Go #o)

). Discussion

This study sho!ed that aceta9olamide did not have significant effect on pain level of the right

shoulder during 2 hours after the operation. ?oehlck et al. () and 6anly et al. (#3) studies

demonstrated that aceta9olamide in%ection can decline referral pain, but not incision pain.

'tatistically significant difference !as not observed regarding referral pain decrease bet!een the

intervention and control groups (, #3).

Tissue acidosis has been introduced as a mechanism of pain creation in Issberner et al. study

(#). 8eduction of venous blood p6 and volume of plasma 6CO& at the same time due to diuretic

effect of 6CO& from kidney has been demonstrated (#2, #&).

ased on 'ingh et al. study, adding aceta9olamide to a multimodal regimen could improve pain

management in patients undergoing laparoscopic nephrectomy (#). 8adhakrishnan et al. (23)

reported that aceta9olamide reverses thermal hyperalgesia !ith an inflammatory origin, but

mechanical allodynia did not change. 'tatistically significant difference !as not observed

bet!een the t!o groups (23). In


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laparoscopy follo!ing administration of aceta9olamide (2#). Our study had some limitations; for

instance, our study !as not blinded.

Overall, aceta9olamide could be effective only in the immediate postoperative period and it had

no confirmed effects on shoulder referral pain follo!ing laparoscopy surgery. 6o!ever, further

studies !ith larger sample si9es are re0uired to confirm this.

Go #o)

Ac!no*ledgments

?e !ould like to ackno!ledge all those !ho helped us !ith this study.

Go #o)

+ootnotesAuthors, Contribution-Reza Movassaghi provided #he h'po#hesis and #he draf#, Ali Peirovifar and Davood

Aghamohammadi %olle%#ed da#a and revised #he final draf#, Hassan Mohammadipour Anvari, Samad EJ Golzariand !ohreh "ourehpaz provided #he revised manus%rip#, %olle%#ed da#a and performed #he anal'sis

Go #o)

References

#. 'okouti


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-. Folahdou9an F, 4ydi


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#. Issberner E, 8eeh $?, 'teen F6. $ain due to tissue acidosisK a mechanism for inflammatory

and ischemic myalgiaS eurosci Dett. #+;23(&)K##G. L$ub

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