Emails on the use of Cytotec, protocols by various places and complicaitons, uterine ruptures, etc
 
on protocols and safety:

Luis Sanchez-Ramos, MD
 

on Uterine  Rupture: Dr. Omar Farag MD.
Assist. Prof. Ob/Gyn,
Faculty of Medicine, Cairo University, Egypt.
Myyer S. Bornstein, M.D., FACOG
Chairman Department of Obs/Gyn
Morton Hospital & Medical Center
88 Washington St. Taunton, MA
Dr Thomas Ind MB BS MD  (X 3) MRCOG
St George Hospital
Kogarah Sydney
NSW 2217 AUSTRALIA
on Amniotic Fluid Embolism:
Clinical Research Fellow
University of Glasgow
Queen Mothers Hospital
Glasgow 
Peter Wein Senior Lecturer
Obstetrics and Gynaecology
University of Melbourne, Mercy Hospital for Women  East Melbourne 3002 Australia
Case report by obstetricans in California

Case Reported by Nurse Midwife

 

 

Date: Thu, 24 Oct 1996
 
Sender: ob-gyn-l@listserv.bcm.tmc.edu
From: mborn <mborn@massmed.org>
To: Multiple recipients of list <
ob-gyn-l@listserv.bcm.tmc.edu>

Subject: Re: Cytotec induction -Reply
List for the discussion of obstetrics and gynecology

Myer:
How about posting your protocol on the list ?  or pleases send me a copy too. But I bet there are several out there who would like to see it.
Dan
 
O.K.  Here it is
Myer

Date:   October 24, 1996
From:   Myer S. Bornstein, M.D., Chief Department of Obstetrics and Gynecology
Subject:    Misoprostol (Cytotec) for Cervical ripening and induction of labor

Misoprostol (Cytotec) is a synthetic PGE1 analogue


For cervical ripening and induction:
 

1. Do NST
2. Insert 25 mcg. tablet in vagina
3. Standard V.S.
4. If patient with prior C/S insert IV and do T&S
5. can repeat dose every four hours up to a total of 6 doses.
6. Pitocin can be started four hours after last dose
7. After three to four hours patient can ambulate.
8. Watch for tachysystole, if occurs remove vaginal tablet  (our cases have not shown any fetal distress)

Second Protocol Oral Dosing
1. Do NST
2. Give 100 mcg. tablet p.o.
3. Standard V.S.
4. If patient with prior C/S insert IV and do T&S
5. Pitocin can be started four hours after last dose
After three to four hours patient can be discharged home and to return if labor ensues of the next day for induction.
 
follow-up email quesiton:
Sender: ob-gyn-l@listserv.bcm.tmc.edu
From: mborn <
mborn@massmed.org>

Any untoward fetal reactions, complications since you have started this protocol? How to you cut the 100 mg tablet? How do you wash it out of the vagina in case of tachysytole? Have you seen much hyperstimulation?
 
Answers:
> occasional fetal tachcardia our pharmacy cuts the tablet (they are 100mcg) since they are in the posterior vagina they can be wiped out with a gloved finger.  we have seen very close contractions without a long resting period,  but there was no fetal abnormal response.  if the patient starts with close contactions we don't give the next dose.

our nurses feel comfortable with our protocol, and  are comfortable about inserting the medication.  this is an easy medication to use and gives great results.
 

Myer S. Bornstein, M.D., FACOG
Chairman Department of Obs/Gyn
Morton Hospital & Medical Center
88 Washington St.
Taunton, MA
mborn@massmed.org

Date: Mon, 8 Mar 1999
 
Sender: ob-gyn-l@obgyn.net
From: @msn.com (RE)
To: Multiple recipients of list <ob-gyn-l@talk.obgyn.net>
Subject: DIC Comment: Obstetrics & Gynecology for Medical Professionals ONLY

Sorry for the length of this post.  I recently had a complicated ob patient that I would like to have your opinions on. 

A 26 y/o primip at term underwent cytotec cervical ripening, receiving three doses over 12 hours.  She was sent home four hours after the third dose and returned the next morning with ruptured membranes, not in labor, 1cm /  50% effaced.

She was placed on pitocin, and had a prolonged latent phase, and a protracted active phase, eventually arresting at 5cm.  During her labor she had intrathecal narcotics x1 after receiving two attempts at epidural placement. 

At the time a C/S was called for, the internal catheter was removed and preparations for C/S were begun.  The pressure transducer was removed and the scalp electrode was inadvertently knocked off the fetus.  Because there had been a normal fetal HR tracing, one was not immediately reapplied. 

The patient was given the usual anesthesia premeds, including reglan and magnesium citrate, and shortly after began to vomit with great force.  The nurses then auscultated a slow fetal HR, I reinserted a scalp electrode, finding a flat FHR of 55-60 (this was 15 minutes after the original electrode dislodged). 

At this point a stat C/S was called for.  The OR crew was already on its way in, the weather was bad, middle of the night, .  .  .  and I practice in a small hospital without in-house OR call

The baby was delivered with APGAR 1, cord ph 6.70, ~25 minutes after stat C/S called. It was transferred to a tertiary care hospital and expired 36 hours later from severe hypoxic encephalopathy

The mother developed a severe postpartum hemorrhage ~45 minutes after completion of the C/S.  The C/S itself was uneventful with no unusual bleeding.  Clotting studies in PACU showed DIC, mother had a very rocky course for the first 24 hours, becoming extremely hypovolemic and oligouric, requiring central monitoring, intubation, 24 units of blood plus many units of FFP, albumin, cryoprecipitate, etc.

At the time of the C/S, I didnít see clinical evidence of abruption, but from my perspective, that would be the most likely cause, precipitated by the forceful vomiting.  Amniotic fluid embolus is another consideration, but I would have expected maternal vital signs to show rapid changes at the time of the emesis. Sepsis is not likely, because even though she had prolonged ROM, she never showed signs of infection.  Any comments would be appreciated.
--
RE. , MD, FACOG
CA, Private Practice 20 yrs.

From: DMECNM@aol.com
Date: Wed, 3 Feb 1999
To: Midwives@lists.alaska.net
Subject: Amniotoic Fluid Embolism (AFE

Considering the latest topics, I just read this from the Perinatal RN list.
 
<<Had my 1st ever amniotic fluid embolus with a 35 year old healthy G3P2. Cytotec had been given twice, 50 mcg., 5 hours apart. 

Patient had hyperstim pattern, reassuring and reactive FHR pattern, no pain, perceived contractions as cramping, palpated by me as moderate. Last dose was 5 hours before seizure. Her membranes ruptured spontaneously  was blood tinged, one small clot; about 70 minutes later, more fluid, clots x 3 within 20 minutes had a seizure.

C/S performed, baby on vent, lived 36 hours. Mother went into DIC, then ARDS, is recovering. Have that gut feeling and it's bad about Cytotec.  The research I've done suggests 25mcg. is plenty.  I've done OB for 16 years and really don't like Cytotec.    Would like to have more discussion re Cytotec.>>
 


Date: Wed, 22 Jul 1998

Sender: ob-gyn-l@obgyn.net
From: 100333.1216@compuserve.com (Thomas Ind)
 
Subject: Misoprostol, hyperstimulation and ruptured uterus with no previous scar
Comment: list for discussion of obstetrics and gynecology

As we have been talking about misoprostol recently I thought I would come online angling for a bit of sympathy.  It's now 04:00am in Sydney and I have just left theatre from a Caesarean section that I started at 21:30 yesterday.

This lady was being induced for post maturity with misoprostol in her second pregnancy.  The head was engaged and the pregnancy was uneventful.  She had a normal previous pregnancy but had had two terminations and a D&C since she was last pregnant.

Her second dose of misoprostol (50ug) went in at 17:00.  At 18:00 I was asked to examine the CTG which had a normal baseline, variabiliy and accelerations with the exception of one small deceleration that occurred with a contraction and lasted a minute.  She was monitored for a further hour on labour ward and the CTG was normal.  As she had an unfavourable cervix and was beginning to contract, I suggested that we repeat the trace in three hours.  When the trace was repeated she was contracting 5 in 10 but with some coupleting and had repetitive variable decelerations with normal reactivity and accelerations.  The cervix was still unfavourable and after discussion we decided to go for a Caesarean Section.  On her way up to theatre, she had a sudden onset of severe abdominal pain and profuse vaginal bleeding.

I did an immediate Caesarean section and delivered a healthy baby. However, the pelvis was full of blood and she had a ruptured uterus into the left broad ligament stretching from the round ligament to the vagina below the level of the insertion of the ureter into the bladder.  To cut a long story short, after primary repair, a Lynch brace suture for uterine atony, correction of coagulopathy, a hysterectomy, involvement of two of my more experienced colleagues and then the vascular surgeons, she is now stable in intensive care.

This was the worst ruptured uterus we had all seen.  My only conclusion is that it was an unusual site to rupture and I wondered whether there may have been previous uterine damage from her terminations.
--
Dr Thomas Ind MB BS MD MRCOG
St George Hospital Kogarah
Sydney NSW 2217
AUSTRALIA

Date: Wed, 22 Jul 1998 20:35:44 -0500
 
Sender: ob-gyn-l@obgyn.net
From: 100333.1216@compuserve.com (Thomas Ind) 
Subject: Re: Misoprostol, hyperstimulation and ruptured uterus with no previous scar
Comment: list for discussion of obstetrics and gynecology

At Wed, 22 Jul 1998, Luis Sanchez-Ramos wrote:
>
>At Wed, 22 Jul 1998, Thomas Ind wrote:
>>As we have been talking about misoprostol recently I thought I would come online angling for a bit of sympathy.
>
Thank you for you sympathy. 

Clearly we will review this case in the cold light of day but I regret that I have just returned from theatre again.  At 06:30 her PT was 16, but the ICU team were having problems with what seemed to be a volume dependent hypotension.  Her platelets were 60 and she had elevated d-dimers so we waited an hour an a half to correct her DIC.  This was done with 10 further units of cryoprecitipitate, 4 of platelets, 4 of FFP and between 05:00 and 07:30 she had a further 10 units of blood (24 in total at this stage). 

Still unable to maintain her circulatory volume with an expanding abdomen we called in the invasivie radiologist but before the team got in her blood pressure became even more difficult to maintain so we took her to theatre and put an Aorta wedge on the aorta.  The vascular surgeon arrived but we were unable to find a single cause of the bleeding.  We tied off five small bleeding areas around the area of the old broad ligament which were homeopathic in size and this along with the cessation of bleeding from aortic compression and further resusitation we have managed to stop the bleeding.

In answer to your questions.  The initial dose was at 09:00.  We would normally have given the second 6 hours later but there was a delay as the whole team were in theatre with another case.  Yes, a 1/4 200ug was used.  We routinely monitor for 20minutes pre-insertion and 60 minutes post-insertion.  When they start complaining of contractions they are monitored again. 

The station was -2, the cervix was medium to firm in consistency, the os did not admit a fingertip, the cervix was 2 cm long and posterior.  She had no USS in the third trimester and therefore no EFW.  Her fundal height at 40/40 was 37cm yet the baby weighed 9lb 13oz (sorry don't understand kilos but this would be a good 4).  She was not contracting at the second insertion and have reviewed the notes and spoken to all concerned to ensure that this was the case.  She is not obese.

--
Dr Thomas Ind MB BS MD MRCOG
St George Hospital
Kogarah, Sydney
NSW 2217 AUSTRALIA

Date: Thu, 23 Jul 1998 03:28:46 -0500
 
Sender: ob-gyn-l@obgyn.net
From: 100333.1216@compuserve.com (Thomas Ind)
 
Subject: Re: Misoprostol, hyperstimulation and ruptured uterus with no
Comment: list for discussion of obstetrics and gynecology

18:00 Sydney time.  We seem to be over the major hurdle now and she is haemodynamically stable.  We have even been able to have a conversation of sorts.  (She is still intubated but has now made me realise what it must be like to be a dentist).

I have had a number of post-mortems of the events with case notes in hand.  So far there have been no major criticisms.

Luis is right though.  These events just do not fit.  However, I suspect we'll never know the answer.  I have asked the histopathologist to look for signs of old scarring but would imagine that this would be difficult in such a specimen.  I will update you.

It is very easy to be scarred for life by such an experience.  I therefore understand Peter's comments.  However, when I was a resident (senior house officer) I worked for two consultants who would not allow the use of Prostin for exactly the same reasons. 
Furthermore, I have seen cases of a ruptured uterus with Prostin, oxytocin and cervagem (for induction of a 20/40 IUD) and I'm sure most of you have as well.

I think it is important to put all these pieces of evidence in prospective.  If we stopped using penicillin because we saw a case of near death from allergy or stopped using the combined pill because we saw a death from pulmonary embolism we would not be advancing in medicine. 

What this case serves to prove is that it is important to be aware of known rare complications and the potential harm any treatment can cause. These all have to be born in mind while making our balanced clinical decision.  In this case the individual risks of induction were balanced against the risks of postmaturity

The decision to use misoprostol was balanced against the use of other induction agents using the best evidence available.  That misoprostol is as safe as other agents and therefore the drug of choice based on cost.  This later point will be reviewed on the basis of this experience as a part of internal audit but the use of misoprostol is unlikely to change unless there is enough new information to change this balance of evidence.

Thank you all for your comments.

--
Dr Thomas Ind MB BS MD MRCOG
St George Hospital
Kogarah Sydney
NSW 2217 AUSTRALIA


Date: Wed, 22 Jul 1998 21:35:41 -0500
 
Sender: ob-gyn-l@obgyn.net
From: sanchez-ramos@worldnet.att.net (Luis Sanchez-Ramos)
 
Subject: Re: Misoprostol, hyperstimulation and ruptured uterus with no
Comment: list for discussion of obstetrics and gynecology

Peter:

Uterine ruptures with serious morbidity and perinatal mortality have occurred with oxytocin, dinoprostone in form of gel, tablets, suppositories etc, gemeprost, and misoprostol. 

Any agent that has uterine contractility properties can lead to this type of catastrophe. We personally have seen more ruptured uteri from other agents than frommisoprostol.  I am sure the same experience is shared by you.

Each adverse event has to be thoroughly studied and causative factors sought.  In the reported ruptures in patients with misoprostol (Obstet Gynecol) several factors other than the use of misoprostol were possible contributors ie, previous cesarean (vertical or classical) use of oxytocin for augmentation, amnioinfusion etc. If after every 5000 inductions with misoprostol one case of uterine rupture is found, then the incidence is not much different than with oxytocin. 

Do you think that oxytocin is a safe drug ? How about Prepidil, Cervidil or any other dinoprostone preparation ? Any oxytocic drug, if not use properly, can lead to serious adverse events.


Luis Sanchez-Ramos, MD

 

At Wed, 22 Jul 1998, Peter Wein wrote:
>
>This case may illustrate a problem about very rare, but very serious adverse reactions to drugs that will not be recognized in any randomized controlled trial, and will only come to light after the drug is extensively used - if misoprostol will do this once in every say 5,000 or so inductions, it is not surprising that it is not seen in the initial
>studies, or in Dr Sanchez-Ramos 2,000 occasions of use. However - if the adverse reaction is life-threatening, even such a rear occurrence my be enough to regard the drug as unsafe.
>
>Not saying that this is the case with misoprostol - but there are similar case reports beginning to appear - and cannot dismiss them as just anecdotes.
>>--
>Peter Wein
>Senior Lecturer
>Department of Obstetrics and Gynaecology
>University of Melbourne, Mercy Hospital for Women
>Clarendon Street, East Melbourne 3002
>Australia >Tel: +61 3 9270 2556 Fax: +61 3 9417 5406 Mobile: 0414 691690

Date: Sun, 10 Jan 1999 09:00:32 -0600
 
Sender: ob-gyn-l@obgyn.net
From: Luis Sanchez-Ramos <
sanchez-ramos@worldnet.att.net>
 
Subject: Re: Cytotec induction/ripening -timing
Comment: Obstetrics & Gynecology for Medical Professionals ONLY
 

At Sat, 9 Jan 1999, Efrain Ramirez MD wrote: >>Do you take the tab out with every tachysystole..even if you have a reassuring FHR pattern?<<
 
Efrain; Good point.  Many physycians tend to get nervous with tachysystole (increased uterine activity without alterations in the FHR).  Under these conditions they give SQ terbutaline or remove the tablet. 

A pattern that is very characteristic with PGE1 is that of frequent uterine activity, of mild to moderate intensity, without alterations in fetal heart rate.  We tend not to intervene in these situations.  We do not, of course, repeat the dose in presence of tachysystole.  It is only in patients whose FHR is abnormal that we intervene with SQ terbutaline or tablet removal. 

Of 33 RCTs published thus far, the only study showing an increase in cesareans was that of Buser et al from St.  Louis.  That trial was performed in a non-university hospital with private practitioners enrolling most of the patients.  As soon as they noted any evidence of increased uterine activity, a cesarean was performed.


LSR
 

Date: Sun, 23 Nov 1997
 
Sender: ob-gyn-l@obgyn.net
From: Peter Wein <
p.wein@obstetrics_mercy.unimelb.EDU.AU>
 
Subject: Re: Misoprostol and uterine rupture
Comment: list for discussion of obstetrics and gynecology

We have had a case of a ruptured uterus using misoprostol for mid-trimester evacuation for FDIU (not yet published).

Every known oxytocic agent has been associated with excessive uterine stimulation and rupture!

At 09:30 PM 23/11/97 -0600, you wrote:
>Is anyone aware of any reports of rupture of a nulligravid uterus with >misoprostol used for cervical ripening (25 micrograms q3-4 hours)?
>
Peter Wein
Senior Lecturer
Department of Obstetrics and Gynaecology
University of Melbourne, Mercy Hospital for Women
Clarendon Street, East Melbourne 3002
Australia  Tel: +61 3 9270 2556 Fax: +61 3 9417 5406 Mobile: 0414 691690



Date: Mon, 24 Nov 1997
 
Sender: ob-gyn-l@obgyn.net
From: ofarag@brainy1.ie-eg.com (Dr. Omar Farag )
 
Subject: Re: Misoprostol and uterine rupture
Comment: list for discussion of obstetrics and gynecology

At Sun, 23 Nov 1997, Larry Glazerman wrote:
>
>Is anyone aware of any reports of rupture of a nulligravid uterus with >misoprostol used for cervical ripening (25 micrograms q3-4 hours)?
 
One day before I posted to the forum an observation about post partum hemorrhage with Misopristol "PP Hge and Misopristol".  The type of bleeding which I encountered looked like an incomplete rupture of the uterus.  It occurred in 3 cases, all multipara.  In two of them, it was life threatening.  Of course any uterine stimulant may be associated with rupture uterus, but here it did not go through a process of obstruction of labor in the classic terms.  In the three cases, it was discovered after labor, during vaginal exploration for post partum hemorrhage.

Dr. Omar Farag MD.
Assist. Prof. Ob/Gyn,
Faculty of Medicine, Cairo University, Egypt.


Bernard Cristalli MD CNGOF
>AIHP - ACCA
>Paris - France
>
http://www.obgyn.net/corresp/cristalli.htm

>What do you mean by "elective" inductions???

>The ACOG definition (hence the one used in the US) is "An induction performed only for the convenience of the Mother or the Physician" ACOG goes on to say that "Elective inductions should not be performed."

>Therefore you are correct the c/s rate for elective induction should be zero, because you should do no elective inductions.

>Ideally, your c/s rate following induction should be about the same as it is following spontaneous labor.

>A 13% CS rate is astonishing. For elective inductions it ought to be 0 ! wait for better Bishops

>In that case I would say Pitocin is very effective to induce C-sections...
>
> Bernard


Reply-To: ob-gyn-l@obgyn.net
 
From: Mahesh Perera <
Mahesh.Perera@clinmed.gla.ac.uk>
 
Subject: Misoprostol and uterine rupture
Comment: list for discussion of obstetrics and gynecology
 

The following are some references that may be helpful
 
1.  Phillips K., Berry c., Mathers AM.,  Uterine rupture during second trimester termination of pregnancy using mifepristone and a prostaglandin. Eur-J-Obstet-Gynecol-Reprod-Biol.  1996 Apr:65(2): 175-6
 
2.  Thong KJ., Lynch P., Baird DT.,  Uterine rupture during therapeutic abortion in the second trimester using mifepristone and prostaglandin (letter; comment) Br-J-Obstet-Gynaecol.  1995 Oct; 102(10): 844-5
 
3. Norman JE., Uterine rupture during therapeutic abortion in the second trimester using mifepristone and prostaglandin   Br-J-Obstet-Gynaecol. 1995 Apr; 102(4): 332-3
 
Hope it would be of help.  Interestingly both case reports are from Glasgow
 
Mahesh Perera
Clinical Research Fellow
University of Glasgow
Queen Mothers Hospital
Glasgow