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Dear listers,
I am increasingly intrigued by drug
behavior in the clinical setting. The acuity in our PICU has risen
dramatically over the past year and a half. We now see much more neuro
trauma, MODS, ARDS and increasingly use CRRT as part of our therapy.
Even if you take the CRRT group out of the mix, I am often
baffled by the
behavior of drugs from an absorption, metabolism and excretion standpoint in
the critically ill child. I have started looking hard for correlations
between drug activity, renal function, liver function, ventilator status
etc. The variables are multifactorial and sometimes independent.
Recently we had a child 13.7Kg who developed sepsis after a
near drowning.
She had a prolonged ventilator course as well. She did suffer a ischemic
encephalopathy secondary to the submersion injury and a mild degree of ARDS.
She was placed on both gentamicin and vancomycin because of
the composition
of the submersion water and her C/S studies. She cleared the gentamicin
quickly and completely. The vancomycin hung around in her serum for
prolonged periods of time. I must interject that she was on dobutamine,
primacor, Nipride, TPN, Versed and Norcuron. All at the same time more or
less.
We dosed the pressors and nipride to effect. The versed and
norcuron were
also dosed using surrogate markers. The doses on all of these drugs
required constant titration.
I ordered levels, poured over the daily labs, monitored urine
output, stool
output, ventilator status using a COSMO and ABGs, stood at the bedside and
pondered for countless hours on what to do next.
The child improved to the point that we are sending her to a
Rehab center
in the morning. She is off the ventilator, pressors etc. I still have no
answers.
I have read a considerable amount of literature in the adult world
concerning SIRS, MODS, ARDS, Sepsis etc. (thank you Mike Darwin and the
CCM-L, and the PICU list)
Ladies and gentlemen, I am stumped. Can any of you suggest articles,
textbooks, personal antidotes, case reports, anything to clear up my
confusion? Are any of you working on the clinical pharmacokinetics of
critically ill children? Are there any plans to do these studies? How would
you start?
I have recently begun to track all of our ICU admissions using a
combination of PIM and an Excel/Access program that I am building.
Any suggestions would be appreciated.
Cheers....... robert
Robert Aucoin, R.Ph.
Senior Clinical Pharm./Operations
The Children's Center at fax 225-765-8410
Our Lady of the Lake RMC raucoin.-a-.ololrmc.com
Baton Rouge, LA. 70809 (toll free)888-765-7428
mraucoin.-at-.bellsouth.net (under construction)
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Date: Mon, 10 Apr 2000 17:42:15 +0200
From: "Dr. Hans-Peter Mayer-Anhalt"
To: PharmPK.-a-.boomer.org
Subject: Re: PharmPK ADME in critically ill child
I think you have problems with anaerobic bacterias. My treatment
suggestion would be, to try artifical respiration in a hyperbaric
chamber with pure oxigen about 2.2 bars, just the way we do it with near
drowned divers. Perhaps you should contact a navy hospital
Robert Aucoin (by way of David_Bourne) schrieb:
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Date: Mon, 10 Apr 2000 14:26:18 -0700
To: PharmPK.aaa.boomer.org
From: Leslie Carstensen Floren
Subject: Re: PharmPK ADME in critically ill child
DEar Dr. Aucoin,
I will begin a PK study in HIV-infected, but not necessarily critically
ill, adolescents at UCSF within the next month and will be happy to share
my findings with you. I am very interested in these questions as well and
would lie to discuss the possibility of collaboration if you are
interested.
Sincerely,
Leslie Carstensen Floren
____
Leslie Carstensen Floren, Pharm.D.
Assistant Professor of Biopharmaceutical Sciences and Clinical Pharmacology
Dept. Biopharmaceutical Sciences, UCSF School of Pharmacy and Div. Clinical
Pharmacology, Dept. Medicine, San Francisco General Hospital
Box 0446
UCSF, SF, CA 94143-0446
voice:(415) 502-4949
---
From: GLDrusano.at.aol.com
Date: Mon, 10 Apr 2000 17:30:58 EDT
Subject: Re: PharmPK ADME in critically ill child
To: PharmPK.-a-.boomer.org
Hi!
Because many of the acute physiological changes that occur in an ICU
environment do not necessarily correlate with observed covariates,
traditional Bayesian methods, even with covariates do not do a good or timely
job for drugs.
Recently, I saw a presentation from David Bayard from the Jet Propulsion Lab
in Pasadena, California where jump functions were employed for this sort of
problem. You may wish to talk to him.
Good luck with this VERY difficult area.
George Drusano
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X-Sender: jelliffe.at.hsc.usc.edu
Date: Mon, 10 Apr 2000 16:37:37 -0700
To: PharmPK.-at-.boomer.org
From: Roger Jelliffe
Subject: Re: PharmPK ADME in critically ill child
Dear Robert:
About critically ill and highly unstable patients, babies, children,
adults, and old folks. We are always interested in developing and enhancing
software to track the behavior of drugs in such patients, and to develop
optimally PRECISE dosage regimens to achieve desired target goals in such
patients. That is why we have developed both parametric (IT2B) and
especially nonparametric (NPEM) approaches to population PK/PD modeling,
and methods for "multiple model" (MM) dosage design. These methods are
discussed in technical reports and publications which are given on our web
site (see below). More recently, David Bayard in our lab has implemented a
sequential Bayesian Interactive Multiple Model (IMM) approach to obtain
Bayesian posterior joint densities in individual patients when their model
parameter values have been changing during the period of data analysis, and
there are no descriptors or covariates to help detect such changes. These
approaches, well known in the aerospace industry for tracking and hitting
hostile targets, are directly applicable to the problem of tracking the
behavior of drugs in highly unstable patients. Take a look at our web site.
I would look forward to talking with you more about these things, as they
are highly important to us, and we are very interested in improving the
therapy of just such patients.
Very best regards,
Roger Jelliffe
Roger W. Jelliffe, M.D. Professor of Medicine, USC
USC Laboratory of Applied Pharmacokinetics
2250 Alcazar St, Los Angeles CA 90033, USA
Phone (323)442-1300, fax (323)442-1302, email= jelliffe.aaa.hsc.usc.edu
Our web site= http://www.usc.edu/hsc/lab_apk
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)