The Perinatal Gazette
Newsletter of the Regional Perinatal Center Maria Fareri Children's Hospital at Westchester Medical Center
Volume 16, Issue 1
Bioethics of Fetal Surgery
PDA Closure in Preterm Infants
Maintenance of the fetal Patent Ductus Arteriosus (PDA) is critical for
Fetal surgery represents a broad spectrum of techniques that are used
diverting circulating blood from the non-breathing lung. Following
to treat birth defects in fetuses in utero. The most common conditions
birth, the closure of a PDA is the normal physiological transition to
treated with fetal surgery are: neural tube defects, congenital dia-
post-natal life. Persistence of the PDA in preterm infants is associated
phragmatic hernias, congenital cystic adenomatoid malformations,
with comorbidities such as pulmonary hemorrhage, Necrotizing En-
congenital heart diseases, pulmonary sequestrations and sacrococcy-
terococcus (NEC), Bronchial Pulmonary Dysplasia (BPD), Retinopathy
geal teratomas.1 There are several categories of fetal surgery: 1.
of Prematurity (ROP), death. Management of the preterm PDA ranges
fetal surgery, a method that involves completely opening the uterus to
from conservative medical management, medical treatment with
operate on the fetus, 2.
Fetendo, an approach that uses real time video
ibuprofen or indomethacin, or surgical ligation. The timing and type
imagery to guide surgical instruments into the uterus to perform sur-
of this intervention is frequently debated. Since these medical and
gery on the fetus, and 3.
Exit procedure, a surgical technique that is
surgical interventions all carry risks to preterm infants, efficacy and
used to deliver babies who have airway compression.
safety of various treatment modalities are often balanced against
The first fetal surgery was performed in 1981 by Dr. Michael Harrison,
possible side effects.
"the father of fetal surgery", at UCSF Children's Hospital.2 He per-
Complicating these treatment approaches is the variable patency
formed a vesicostomy for congenital hydronephrosis. After this first
based on gestational age. Approximately 80% of premature infants
fetal operation, new techniques with less invasive forms have allowed
who are greater than or equal to 29 weeks at birth will achieve sponta-
additional defects to be treated.
neous permanent closure of their PDAs. It seems reasonable to man-
A milestone in the history of fetal surgery is the MOMS trial. This was a
age these infants conservatively-e.g., allow their PDAs to close, and
multicenter randomized trial of prenatal versus postnatal repair of my-
only intervene if they become hemodynamically significant. For pre-
elomeningocele done in 2002. According to this trial, prenatal surgery
mature infants born at 28 weeks or younger, the rates of spontaneous
for myelomeningocele reduced the need for shunting and improved
permanent closure drop to below 40%; and drop to approximately
motor outcomes at thirty months but was associated with maternal
10% for 24-week preterm infants and below. The PDAs of ELGANs (ex-
and fetal risks. The success of this trial inspired formation of The North
tremely low gestational newborns < 28 weeks gestation) may there-
American Fetal Therapy Network (NAFTNet) in 2005 to promote multi-
fore be more suitable targets for medical treatment interventions. The
institutional trials on fetal surgery in the United States and Canada.
current medications FDA-approved for treatment of PDA in preterm infants include intravenous ibuprofen lysine (Neoprofen®) and intra-
Open Fetal Surgery Technique
venous indomethacin (Indocin®). As with any medication, there may
Any type of fetal surgery requires a multidisciplinary approach includ-
be side effects, which for these medications may include changes in
ing pediatric surgeons, obstetricians, neonatologists, radiologists and
platelet function, as well as variable degrees of gastrointestinal and
anesthesiologists. Open fetal surgery involves administration of gen-
renal toxicity. In the search for other medications for PDA closure, en-
eral anesthesia to the mother in which the anesthetic agent crosses
teral formulations have been utilized with variable success, and an ob-
the placenta and the fetus receives satisfactory anesthesia. To control
servational study published in 2011 by Hammerman et al., identified
and prevent labor, tocolytics are used during and after surgery. The
enterally-administered paracetamol as a possible alternative for PDA
uterus is exposed with an abdominal incision and then it is lifted up.
closure in preterm infants. / Continued page 2.
Subsequently, another incision is made in the uterus to expose the fetus to access and perform the surgery. The fetus remains connected
INSIDE THIS ISSUE
to the placenta throughout the procedure. Once the surgery is completed, the fetus is returned to the uterus and the amniotic fluid is
1. Paracetamol Treatment for PDA Closure In Preterm Infants
replaced. Then, the uterus is sutured and put back in the abdomen.
/ Continued on p. 2
Finally, the abdominal incision is closed. After surgery, the mother and
1. Bioethics of Fetal Surgery / Continued on p. 3
the fetus are kept under observation. The infant is usually delivered 3
4. 4th Annual Regional Perinatal Public Health Conference
/ Continued page 3.
Continued from page 1, Paracetamol Treatment
Continued from previous column
Paracetamol is well-tolerated by infants and children for its analgesic
glutathione level did not decrease over time, and the AST/ALT levels
eff ects and may be used post-operatively in NICU settings. It is best
were not signifi cantly elevated above 50 U/l. They also found that se-
known for pain control mediated through the central nervous system.
rum paracetamol reached steady state around 31 hours after the fi rst
However, the use of paracetamol for PDA closure is a relatively new
dose, and the metabolism changed with gestational age. Ganzewin-
medication, and there is very limited data for safety and effi cacy in
kel also concluded that clearance of paracetamol increased with post-
this ELGAN patient population. There are currently two proposed
menstrual age as well as with increasing birth weight. Though these
mechanisms of action for paracetamol-mediated closure of PDA.
numbers are promising in terms of the safety of IV paracetamol, it is
Prostaglandin H2 synthetase (PGH2 synthetase) has two components,
still unknown if the more available and less expensive oral form of
the cyclooxygenase (COX) component and the peroxidase (POX)
paracetamol shares the same bioavailability and pharmacokinetics as
component. One theory claims that paracetamol directly inactivates
the IV form; and, whether this is effi cacious in PDA closure in ELGANs.
the COX component. The other hypothesis proposes that paracetamol
Paracetamol is a drug used by neonatologists for pain control in pre-
inactivates the POX component, which blocks the transformation of
term infants; however, the proposed application of oral paracetamol
prostaglandin G2 (PGG2) to prostaglandin H2 (PGH2) (Figure 1).
for PDA closure is relatively new. With limited data on safety and ef-
fi cacy of paracetamol (particularly enterally-administered) use in ELGANs, and in particular when used for treatment of PDA, it would seem that caution should be exercised. Pharmacokinetics following
enteral administration, comparisons to established safety and effi cacy profi les of IV ibuprofen and IV indomethacin, particularly in ELGANs,
would seem to be prudent before oral paracetamol achieves another medical treatment for PDA closure of ELGANs.
Jennifer Hsu, MD, Neonatal Fellow, WMC
Lance Parton, MD, Attending Neonatologist, WMC
There are no studies that address the safety and effi cacy of paracetamol use in preterm infants. It is known that high serum paracetamol levels may cause a direct hepatotoxic insult from its me-
tabolite. Paracetamol is metabolized in the body via UDP-glucurono-
Koch et al "Prevalence of spontaneous closure of the ductus arteriosus in neonates at
syltransferase 1A6 enzyme into paracetamol-glucuronide (APAP-G)
birth weight of 1000 grams or less" Pediatrics, vol 117, number 4, April 2006
and paracetamol–sulphates (APAP-S), 1-4% is excreted unchanged
Clyman "Mechanism regulating the ductus arteriosus" Biol Neo 2006; 89:330-335
through the kidneys, and 8-10% is further oxidized to 3-hydroxyl
Lucas et al. "Cellular mechanisms of acetaminophen: role of cyclooxygenase" FASEB
paracetamol and N-acetyl-p-benzo-quinone-imine (NAPQI) via liver
Allergaert et al. "Paracetamol to induce ductus arteriosus closure: is it valid?"Arch Dis
cytochrome P450 2E1. It is this NAPQI metabolite that has a direct tox-
ic eff ect on hepatocytes (seen in acetaminophen overdose). When the
E Nadir et al. "Paracetamol treatment of patent ductus arteriosus in preterm infants"
Journal of Perinatology (2014) 34, 748-749
serum level of paracetamol is within range, endogenous glutathione
Yurttutan, et al. "A diff erent fi rst-choice drug in the medical management of patent
further conjugates NAPQI into cysteine and mercaptic acid into non-
ductus arteriosus: oral paracetamol" J Maternal Fetal Neonatal Med, 2013; 26(8)L
toxic forms that are excreted. It has been proposed that when increas-
ing serum paracetamol levels overwhelm endogenous glutathione,
Dang et al. "Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants
with Patent Ductus Arteriosus: A Randomized Controlled Trial" PLOS ONE November
NAPQI accumulates and acts directly on hepatocytes, and manifests
2013 Volume 8 Issue 11 e77888
as liver injury with elevated aspartate transaminase (AST) and alanine
Oncel et al "Oral Paracetamol versus Oral Ibuprofen in the Management of Patent
transaminase (ALT) levels.
Ductus Arteriosus in Preterm Infants: A Randomized Controlled Trial" J Peds, Vol. 164,
No. 3 March 2014
Though there are studies that are currently in print claiming success
Dash et al. "Enteral paracetamol or Intravenous Indomethacin for Closure of Patent
Ductus Arteriosus in Preterm Neonates:A Randomized Controlled Trial" Indian Pediat-
of PDA closure using paracetamol, these studies are mainly observa-
rics, Vol 52, July 15, 2015
tional, with small patient numbers, using diff erent dosages (ranging
Rolland et al "Natural evolution of patent ductus arteriosus in the extremely preterm
from oral 7.5 -15mg/kg/dose q6h) with variable treatment durations
infant"Arch Dis Child Fetal Neonatal Ed 2015;100:F55–F58.
(ranging from 3-7days). The subjects were more mature preterm in-
Pacifi ci et al. "Clinical Pharmacology of Paracetamol in Neonates: A Review" Current
Therapeutic Research 77 (2015) 24–30
fants, who were born with birth weights above 1 kg. One of the major
Ganzewinkel et al "Multiple intravenous doses of paracetamol result in a predictable
criticisms for these studies is that the background spontaneous clo-
pharmacokinetic profi le in very preterm infants" Acta Pædiatrica 2014
sure rates were not taken into consideration. Therefore it is unknown
Kluckow et al. "A randomised placebo-controlled trial of early treatment of the patent
ductus arteriosus" Arch Dis Child Fetal Neonatal Ed 2014;99:F99–F104. doi:10.1136/
from these studies whether paracetamol is truly eff ective in facilitat-
ing closure of PDA.
Rozé et al. "Association Between Early Screening for Patent Ductus Arteriosus and In-
Hospital Mortality Among Extremely Preterm Infants" JAMA. 2015;313(24):2441-2448.
Currently the eff ective serum level for PDA closure in preterm infants
with paracetamol has yet to be established. In addition, potential
Koch J. et al. Pediatrics.2006;117: 1113-1121
hepatotoxicity eff ects have not been investigated in preterm infants.
Clyman RI. "Ibuprofen and patent ductus arteriosus". N Engl J Med 2000; 343:
To address the issues of serum steady state elimination, and toxicity
Irena Kessel et al. "Paracetamol eff ectiveness, safety and blood level monitoring dur-
of paracetamol in preterm infants, Ganzewinkel et al investigated
ing patent ductus arteriosus closure: a case series". J Matern Fetal Neonatal Med, Early
the pharmacokinetics of paracetamol (IV) when given for pain con-
Online: 1–3 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2013.871630
trol. Fifteen preterm infants born less then 32 weeks gestational age
Afi f El-Khuff ash et al. "Effi cacy of paracetamol on patent ductus arteriosus closure
may be dose dependent: evidence from human and murine studies" Pediatric Re-
were given fi ve repeated doses (7.5mg/kg/dose) of IV paracetamol for
SeARCh Volume 76 Number 3 September 2014
pain control. They found that with repeated IV doses, the endogenous
Gianluca Terrin et al. "Effi cacy of paracetamol for the treatment of patent ductus
arteriosus in preterm neonates" Italian Journal of Pediatrics 2014, 40:21
Continued next column
Continued from page 1, Bioethics of Fetal Surgery
Continued from previous column
by planned caesarian section at approximately 36 weeks gestation,
is viable, the needs of the fetus may take precedence over the wishes of
unless premature labor or other complications occur before that time.3
the pregnant woman. If the fetus is not viable, the pregnant woman's
decision should be respected.
Bioethical aspects of fetal surgery
The pregnant woman should be allowed the freedom to decide upon
One ethical consideration for the clinician with fetal surgery is to assess
alternative courses of therapy based on her values and beliefs10. How-
the benefits and risks of the procedure to both pregnant woman and the
ever, society expects that pregnant women to be altruistic. The ideas of
fetus. The clinician should respect the autonomy of the pregnant wom-
maternal altruism do not fit into an autonomy-based ethic system.11
an and obtain informed consent for the procedure 4,5 The consent should be taken by a physician competent to explain the intervention and its
Another potential conflict can arise when the maternal and paternal de-
alternatives with its risks and benefits. The consent should be non-direc-
sires are not the same. US federal regulations are distinctive in the inter-
tive and should avoid therapeutic misconception.
national context in continuing to require the consent of the father for fetal research, including maternal fetal surgery. This allows undue influ-
The mother, the fetus, the physicians and on a larger scale the society
ence or even control over the pregnant woman's autonomy by someone
may benefit from fetal surgery. Fetal surgery might mitigate the anxiety
who bears none of the medical risks. The ACOG Committee Opinion is as
for the mother caused by awaiting the birth of a fetus with known med-
follows: "Although it may be appropriate and helpful for the father to be
ical problems. Fetal surgery can also improve the condition of the fetus
involved in these decisions and have complete access to information, to
or it can possibly prevent its death. The physicians may be relieved to act
assign him any authority to assent or dissent would unjustifiably erode
upon a known fetal threatening diagnosis. There could also be a de-
the autonomous decision-making capacity of the pregnant woman."
crease in the burden of sick or disabled people to the society.
Progress in medical practice depends on innovation; however surgery
All these benefits have to be balanced with the risks of the procedure.
on the fetus is always surgery on the pregnant woman as well. Ethical
The overall perinatal mortality after open surgery has been estimated to
obligations to both must be taken into account in the design and con-
be approximately 6%. The safety depends on the specific procedure, the
duct of research on maternal-fetal surgery.
gestational age and the condition of the fetus. The costs of the proce-dure have to be taken into account as well.
In conclusion, fetal surgery is still not yet standard of care and
can be justified when:
The specific risks for the pregnant woman in open fetal surgery include: uterine rupture, additional C-sections, premature labor and delivery, ex-
(1) There is reasonable certainty that the fetus will suffer irrevocable
posure to multiple drugs and prolonged hospitalization. The risks for the
and substantial harm without the intervention;
fetus involve premature delivery, exposure to anesthesia, failure of sur-
(2) The intervention has been shown to be effective and it has a realistic
gery and fetal demise6. There is a risk of incremental harm from inter-
chance of saving the life of the fetus or preventing serious and irre-
vention, possibility of iatrogenic versus natural disability, a child with a
versible disease and disability.
severe disability versus a child with milder disabilities or no child.
(3) The risk to the health and well-being of the pregnant woman
In summary, the trade-offs for the pregnant woman who has a fetal can-
didate for surgery include: her risks versus her benefits, her fetus's risks versus her fetus's benefits, her risks versus her fetus's benefits and her
(4) The pregnant woman can give appropriate informed consent to the
fetus's risks versus her benefits.
The physicians have obligations to the fetus as well as to the expecting
Cosmina Mandru, MD, Neonatal Fellow, WMC
mother. An ethical dilemma exists when the desires of the mother op-
pose needs of her fetus. This dilemma is resolved by taking into consid-eration the viability of the fetus. Viability is defined as the ability of the
Semsa Gogcu, MD Attending Neonatologist, WMC
fetus to exist ex utero with or without technological support. If the fetus / Continued next column
1. Adzick, NS; Thom EA, Spong CY, Brock III JW, Burrows PK, Johnson MP, Howell LJ, Farrell
JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL "A Random-
ized Trial of Prenatal versus Postnatal Repair of Myelomeningocele". New England
Journal of Medicine 364 (11): 993–1004
2. Jancelewicz, T; Harrison, M "A history of fetal surgery" Clin Perinatol,
3. Sutton LN. "Fetal surgery for neural tube defects".
Best Pract Res Clin Obstet Gynaecol 22 (1): 175–88.
4. Beauchamp, T; Childress, J -Principles of Biomedical Ethics 38 (4th ed. 1994)5. Chervenak, F; McCullough, L "A Practical Method of Analysis of Obligations to Mother
and Fetus". Perinatal Ethics 66 OBSTETRICS & GYNECOLOGY 442 (1985).
6. Johnson, M. P.; Sutton, L. N.; Rintoul, N.; Crombleholme, T. M.; Flake, A. W.; Howell, L. J.;
Hedrick, H. L.; Wilson, R. D.; Adzick, N. S. (2003). "Fetal myelomeningocele repair: short-
term clinical outcomes". American journal of obstetrics and gynecology 189
7. E. F. Werner at al. "Evaluating the cost-effectiveness of prenatal surgery for myelomenin-
gocele: a decision analysis" Ultrasound Obstet Gynecol 2012; 40: 158–164
8. Fasouliotis, S.J. & Schenker, J.G." Maternal-fetal conflict" Eur. J. Obstet. Gynecol. Reprod.
Biol. 89, 101-107 (2000).
9. Oduncu, F.S., Kimmig, R., Hepp, H. & Emmerich, B "Cancer in pregnancy: maternal-fetal
conflict" J. Cancer Res. Clin. Oncol. 129, 133-146 (2003).
10. Isaacs, D. "Moral status of the fetus: fetal rights or maternal autonomy?" J. Paediatr. Child
Health 39, 58-59 (2003).
11. Anna Smajdor "Ethical challenges in fetal surgery" J Med Ethics 2011;3712. American College of Obstetricians and Gynecologists, Committee on Ethics. ACOG
Committee Opinion No. 377: research involving women. Obstet Gynecol. 2007;110(3):
14th Annual Hudson Valley
to predict heart disease, how research and collaboration can be fa-
Regional Perinatal Public Health cilitated through social media, and the necessity of responsible social
The afternoon keynote presentation was delivered by Jermane Bond,
PHD, Program Director, Boys & Men of Color, National Collaborative
The 14th annual Hudson Valley Regional Perinatal Public Health
for Health Equity. Dr. Bond presented "The Paternal Factor: Evidence,
Conference, "Hot Topics in Perinatal Health: Social Media, Donor
Strategies, & Innovations,"
a talk focused on the important role of pa-
Milk, Paternal Impact, and Reproductive Environmental Health"
ternal involvement in pregnancy. The session touched on historical
was held November 4th, 2015 at the DoubleTree in Tarrytown, NY.
and contemporary aspects of fatherlessness, related socioeconomic
The conference was hosted by the Regional Perinatal Center at Ma-
factors, and recommendations to better involve fathers, as well as re-
ria Fareri Children's Hospital(MFCH)/Westchester Medical Center
search on paternal impact.
Health Network, the Lower Hudson Valley Perinatal Network (LHVPN)
Dr. Boriana Parvez, Medical Director, Donor Preterm Human Milk
and Maternal Infant Services Network with major sponsorship from
Bank, Westchester Medical Center Health Network, presented
Children's Health & Research Foundation and March of Dimes. Over
"Benefits of Donor Milk in the NICU"
, a talk focused on the impor-
120 health, medical and human services professionals from the sev-
tance of breastfeeding and how to increase rates. She described how
en counties of the Lower Hudson Valley attended.
donor milk banks help improve short and long term outcomes of
Dr. Michael Gewitz, William Russell McCurdy Physician-in Chief; Chief,
both infants and mothers. Initial results at MFCH showed significant
Pediatric Cardiology, Maria Fareri Children's Hospital, gave the wel-
improvements in breastfeeding as a result of donor milk availability.
coming remarks commenting on the importance of public health
Dr. Edmund F. La Gamma, FAAP, Chief, Division of Newborn Medi-
conferences in shaping healthcare and reaching communities.
cine, Professor of Pediatrics, Biochemistry and Molecular Biology,
The first speaker of the day was Dr. Andrew Elimian, FACOG, Profes-
NY Medical College; Chief, Regional Neonatal Center, Maria Fareri
sor, OB/GYN, NY Medical College; Director, Maternal Fetal Medicine,
Children's Hospital at WMC presented "State of the Region's Perina-
WMC, who presented "Premature Birth: Can it be Prevented?"
tal Health". He spoke on national trends in births, prematurity and
talk focused on causes, pathways, and trends of preterm birth. Dr.
related ethical issues, breastfeeding, and drug related discharges. Dr.
Elimian addressed the global impact of prematurity and the numer-
La Gamma touched on the RPC at WMC and its role as a referral cen-
ous international prevention efforts.
ter for the region, as well as various NYS DOH public health initiatives.
Dr. La Gamma also spoke briefly about the emerging problem of high
The morning keynote speaker was Dr. Marya G. Zlatnik, MMS, Associ-
rates of survival just below the upper limit of a legal termination of
ate Director, Maternal Fetal Health & the Environment, UCSF-Western
pregnancy at 24 weeks gestation and how this represents a paradox
States Pediatric Environmental Health Specialty Unit, presenting
for clinicians in the delivery room regarding whether a child's right to
"Environmental Contaminants & Reproductive Health: What Should
a trial of therapy as valued by the provider can be superseded by a
We Tell Women?"
Dr. Zlatnik addressed the increase in chemicals
parental right to decline care. The option of delivery room hospice
in our everyday lives, their potentially harmful role in reproduc-
was discussed as a compromise position in extraordinary circum-
tive health, and how to counsel pregnant women regarding these
stances where no clear path to reconciliation materializes.
environmental hazards. She concluded her talk with 10 easy to fol-
low steps on avoiding contaminants, such as which foods to choose
Closing remarks were made by Cheryl Hunter-Grant, LMSW, CLC,
based on likely levels of pesticide residuals, organic vs. non-organic.
Executive Director, LHVPN. Her take-home message was one of col-
laboration on all fronts in an effort to provide access to health care
The late morning keynote speaker, Dr. Nathaniel DeNicola, MSHP, FA-
and promote health equity toward improving perinatal health out-
COG, Faculty in Obstetrics & Gynecology at University of Pennsylva-
comes throughout our region.
nia; Senior Fellow, Penn Social Media & Health Innovation Lab,
presented "The Doctor Will Tweet You Now: Professional Use of Digi-
David Aboudi, BA, Data Manager, Regional Perinatal Center, WMC
tal & Social Media in Public Health Advocacy"
. Dr. DeNicola discussed
the role of social media in healthcare, including online data being used
/ Continued next column.
We are interested in providing you with a newsletter that is
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relevant and of interest to you. Please contact us with perinatal
for information about the Regional Perinatal Center at the
topics you would like to see addressed.
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Team & Perinatal Gazette
Professor & Chairman of the
FAAP, Associate Director
Maternal Fetal Medicine, Dept.
Department of Obstetrics &
Regional Perinatal Center
OB/GYN (914) 493-2250
Gynecology (914) 594-2113
MD, FACOG Chief
Data Collection (914) 493-8309
R.N., M.S., Editor,
of Perinatal Medicine, Department
Director Newborn Medicine &
Coordinator, Regional Perinatal
of Obstetrics and Gynecology
RPC (914) 493-8558
Center (914) 493-8590
The Regional Perinatal CenterMaria Fareri Children's Hospital At Westchester Medical Center100 Woods Road, Valhalla, New York 10595
J Korean Neurosurg Soc 43 : 143-148, 2008 Incidence and Risk Factors of Acute Yoon-Sik Oh, M.D.1 Postoperative Delirium in Geriatric Dong-Won Kim, M.D.2 Hyoung-Joon Chun, M.D.1 Hyeong-Joong Yi, M.D.1 Objective : Postoperative delirium (POD) is characterized by an acute change in cognitive function and canresult in longer hospital stays, higher morbidity rates, and more frequent discharges to long-term care facilities.In this study, we investigated the incidence and risk factors of POD in 224 patients older than 70 years ofage, who had undergone a neurosurgical operation in the last two years.Methods : Data related to preoperative factors (male gender, >70 years, previous dementia or delirium, alcoholabuse, serum levels of sodium, potassium and glucose, and co-morbidities), perioperative factors (type ofsurgery and anesthesia, and duration of surgery) and postoperative data (length of stay in recovery room,severity of pain and use of opioid analgesics) were retrospectively collected and statistically analyzed.Results : POD appeared in 48 patients (21.4%) by postoperative day 3. When we excluded 26 patients with
Antidepressant Pharmacology – An Overview Figure 1. Source: NEJM 2005;353:1819-34 Figure 2. Sue Corrigan, BScPharm, ACPR, Pharm D Clinical Pharmacy Specialist, SMH December 2011 Figure 3: Antidepressant Pharmacology pictures: NOTE: CYP enzymes noted are those inhibited by the Source: Stephen Stahl - Essential Psychopharmacology