Download Notes: Notes: Objective: Demonstrate knowledge of the principles of

Notes:
Dangerous on its own...
or in combination
CASE FOUR
Dr. Maude St-Onge
Dr. Dominique Piquette
Notes:
Objective:
Demonstrate knowledge of
the principles of clinical
pharmacology, frequent
drug interactions and their
prevention/management.
PART ONE
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Notes:
It is Tuesday night and you are on call for the ICU.
You don't really mind because it has been one of
those dark and humid days of November. At 3:00
AM, you get called by the Rapid Response Team
(CRRT) nurse for your assistance. She is on the
medicine floor assessing a 75-year-old patient
admitted 24 hours ago for possible urosepsis. The
patient is now obtunded, tachycardic, tachypneic
and has a fever at 41.1oC. The CRRT nurse informs
you that the story is actually quite obscure.
Notes:
“The patient was found by the police on the
street. Nobody could provide any information
about his past medical history or his
medication. Unfortunately, the Medicine Team
could not obtain any details from the patient
himself because he was very confused on
admission. No record of previous admission to
this hospital was available and no contact
information was found.”
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Notes:
When the Medicine Team first saw the patient in
the Emergency Department, the patient was
tachycardic at 120/min and hyperthermic
(40oC). His BP and saturation were normal. His
blood sugar was 11 mmol/L. His urine looked
cloudy and the Medicine Team thought he was
probably septic from a urinary source because
his chest x-ray was unremarkable.
Notes:
Blood work and pancultures were sent and the
patient was empirically treated with PIP-TAZO. A
CT scan of his head was ordered to look for other
sources of confusion, but only showed signs of
remote strokes. Earlier this evening, the
Medicine Team was unable to perform a lumbar
puncture because of patient's lack of
cooperation. Even with two persons holding him,
they were not able to position him correctly.
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Notes:
“I’m worried about our Mr. Dos here
because of some abnormal
movements of the body that I
noticed when I arrived. I’m really not
sure if it was rigors, tremors, or
seizures. The patient is mostly
agitated now.”
The patient’s current vital signs are:
RR: 36/min
HR: 140/min
BP: 100/50 mmHg
Sat 93% (6L/min)
Temp: 41.1oC
BS: 13 mmol/L
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Notes:
An ECG was done and showed, according to the
Medicine resident, a sinus tachycardia. The CRRT
nurse concludes by saying:
Notes:
“Can you please come
and assess this
patient? I’m not
comfortable leaving
him on the ward.”
Notes:
Objectives:
- Discuss the differential
diagnosis of hyperthermia.
- Discuss the risk factors
and the clinical presentation
of the following diagnosis:
serotonin syndrome,
neuroleptic malignant
syndrome, anticholinergic
toxicity, malignant
hyperthermia.
- Describe the management
of undifferentiated severe
hyperthermia.
PROPERTIES
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QUESTIONS:
- Which non-infectious
etiology(ies) could explain
this patient's hyperthermia?
- Assuming that the etiology
of this patient's fever is
infectious, which sources
would you include in your
differential diagnosis?
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- How does the presence of
neurological symptoms
influence your differential
diagnosis?
- Which clinical findings
would you look for during
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your physical exam?
- Would you treat
symptomatically the
hyperthermia?
- Why?
Notes:
PART TWO
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A few minutes later, you arrive at the bedside to
evaluate the patient. You perform a physical
examination.
The patient has good bilateral air entry with normal
heart sounds. His abdomen is soft with normal bowel
sounds. He is warm to touch with bouncing pulses. He is
diaphoretic and has no skin mark or lesion.
The pupils are 5 mm and reactive, with no cranial nerve
deficit. He has spontaneous tremors, hyperreflexia
predominant in the lower limbs, and inducible clonus.
You don’t notice any focal neurological finding. The
muscle tone is hard to assess because the patient
doesn't collaborate. You can't flex his neck.
The results of the blood work done by the CRRT
nurse 30 minutes ago are back:
Blood Gas Type
pH
pCO2
pO2
Bicarbonate
Saturation
FiO2
CBC
Hemoglobin
WBC Count
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Platelet Count
Hematocrit
ARTERIAL
7.30
20
85
15
0.93
?
7.35 - 7.45
35 - 45 mm Hg
80 - 100 mm Hg
21 - 28 mmol/L
0.90 - 1.00
120
13.4
10.3
3
0.6
0
0.1
250
0.400
115 - 165 g/L
4.0 - 11.0 x 10E9/L
2.0 - 7.5 x 10E9/L
1.0 - 4.0 x 10E9/L
0 - 1.0 x 10E9/L
0 - 0.7 x 10E9/L
0 x 0.3 x 10E9/L
150 - 400 x 10E9/L
0.340 - 0.490 L/L
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Notes:
Notes:
Notes:
Calcium Profile
Calcium
Magnesium
Phosphate
Albumin
2.38
0.60
0.65
25
2.20 - 2.60 mmol/L
0.70 - 1.05 mmol/L
0.87 - 1.52 mmol/L
35 - 50 g/L
Electrolytes
Sodium
Potassium
Chloride
CO2 Total
135
4.0
110
15
135 - 147 mmol/L
3.5 - 5.0 mmol/L
95 - 107 mmol/L
22 - 30 mmol/L
Glucose- Random
14.0
4.0 - 8.0 mmol/L
INR
PTT
1.2
32.0
0.9 - 1.10 INR
24.0 - 34.0 SECS
Renal Profile
Urea
Creatinine
5.5
90
3.0 - 7.0 mmol/L
44 - 106 umol/L
Notes:
CK + CK-MB
CK
850
< 195 IU/L
4
2- 6 ng/mL
<0.01
< 0.05
Troponin T
0.07
< 0.10 ug/L
Lactate - Serum
1.2
0.5 - 2.0 mmol/L
Bilirubin - Total
18
<20.0 umol/L
AST
55
<31 IU/L
ALT
40
<31 IU/L
ALP
118
40 – 120 IU/L
mB Mass
mB Mass Fraction
Liver Profile
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Notes:
YESTERDAY - EMERGENCY DEPARTMENT
Blood Gas Type
pH
pCO2
pO2
Bicarbonate
Saturation
FiO2
ARTERIAL
7.33
25
85
18
0.93
?
7.35 - 7.45
35 - 45 mm Hg
80 - 100 mm Hg
21 - 28 mmol/L
0.90 - 1.00
Electrolytes
Sodium
Potassium
Chloride
CO2 Total
136
3.8
108
18
135 - 147 mmol/L
3.5 - 5.0 mmol/L
95 - 107 mmol/L
22 - 30 mmol/L
Glucose- Random
10.0
4.0 - 8.0 mmol/L
Notes:
Renal Profile
Urea
5.0
3.0 - 7.0 mmol/L
Creatinine
80
44 - 106 umol/L
Lactate - Serum
1.0
0.5 - 2.0 mmol/L
Salicylates
<1.0
<1.0 mmol/L
Ethanol
10
0 mmol/L
Osmolarity
300
280-300 Osm/L
Tox screen (urine)
negative
N.B.: A TSH was sent in the Emergency Room and is normal.
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Notes:
The CRRT nurse has already inserted a Foley
catheter and two 16-gauge peripheral IVs. A liter
of normal saline is almost finished. You agree
with the nurse that the patient needs to come to
the ICU. You are wondering if you should
intubate him and sedate him to do the lumbar
puncture.
While the transfer is being organized, you ask
the nurse to give another bolus of fluid, to
administer some IV thiamine, and to give some
IV antibiotics for meningitis.
Notes:
You notice in the chart that the social worker
and the pharmacist were able to reach the
shelter where Mr. Dos lives. He was known for
substance abuse disorder (amphetamines,
heroin, LSD, alcohol) and was recently started on
Fluphenazine for a psychotic disorder (but was
poorly compliant).
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Notes:
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Objectives:
- Differentiate
pharmacodynamic
interactions (additive effect,
synergistic effect, antagonist
effect) from pharmacokinetic
interactions (absorption,
distribution, metabolism,
excretion).
- Identify which
drugs/substances/interaction
s can give a serotonin
syndrome and discuss by
which mechanism.
- Identify which drugs can
give a neuroleptic malignant
syndrome and discuss the
potential pathogenesis.
- Identify which
drugs/substances can cause
withdrawal syndrome and
discuss by which
mechanism.
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Questions:
- How worried are you about
this patient?
- How do you explain his
metabolic acidosis?
- How is the information
provided by the pharmacist
and social worker helpful?
- Have you modified your
working diagnosis at this
point?
- Could you discuss the
pharmacodynamic and
pharmacokinetic interactions
relevant for this patient?
- How would you find
additional information on this
topic if necessary?
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Notes:
PART THREE
Notes:
A few hours later, the patient has been intubated
and sedated. A new attempt at performing the
lumbar puncture was unsuccessful because the
patient was very stiff and couldn't be properly
positioned. At the end, you paralyzed the patient
to complete the procedure.
The patient's heart rate is now 120/min (sinus
rhythm), the blood pressure is 110/55 mmHg,
and the temperature is 39oC despite the cooling
blanket. His latest CK level is 10 000 IU/L with
positive myoglobinuria. The preliminary results
of the lumbar puncture are non-contributory.
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Notes:
You decide to call the Poison Control Center, who
suggests to treat this patient for neuroleptic
malignant syndrome with Dantrolene. They also
suggest to add Cyproheptadine in case of a
serotonin syndrome. You also increase the
Midazolam infusion and add a Propofol infusion.
Over the next 4h, the patient seems to respond
well to the Dantrolene administration. He
becomes less rigid and the temperature drops to
38oC.
Notes:
Around 7:00 AM, just when you think that you
are getting things under control, the patient
develops a rapid unstable atrial fibrillation. You
cardiovert him and he returns into sinus rhythm
at 110/min with occasional short runs of atrial
fibrillation up to 180/min.
You decide that your last contribution to his care
(at least for this call) will be a loading dose of
Amiodarone (150 mg) followed by an IV infusion.
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Notes:
You wake up around 12:30 pm on your post-call
day thinking...
“Shoot! Did I order any medication that could
make the patient's condition even worse??”
Notes:
When you see the patient 24h later, he is still
sedated and no longer rigid. His CK level is
decreasing. However, his FiO2 requirements have
increased and his chest X-ray shows signs of
pulmonary edema. His blood pressure is 100/70
mmHg. His ECG follows:
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Notes:
Questions:
- How would you measure
the QT interval of this
patient? Is it normal?
- Can you describe the
rhythm? How would you
manage the patient at this
point?
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Notes:
You notice that a bedside 2D echo was performed
yesterday and documented a decreased left
ventricular function although difficult to assess
because of the atrial fibrillation. The IVC was
measured at 2 cm and was not collapsing easily.
The central venous saturation is currently 65%. The
fluid balance is now positive by 6L. The patient has
a good urine output and does not demonstrate any
sign of organ hypoperfusion. His magnesium level is
normal, but his potassium is 5.6 mmol/L. He is
afebrile and all cultures have been negative thus far.
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Notes:
You decide to add Digoxin to his medication.
However, you are concerned about potential
interactions with other medications. The ICU
pharmacist is sadly on vacation this week. You
also need to decide if this patient needs to be
started on Warfarin.
Notes:
Objectives:
- Identify risk factors for drug
interactions in the ICU.
- Identify frequent drug
interactions with
Amiodarone and Digoxin, by
which mechanisms they
occur and how to prevent it.
- Identify which drugs can
cause hyperkalemia and by
which mechanisms.
- Identify which drugs can
prolong QTc.
- Identify frequent drug
interactions with Warfarin
and how to prevent it.
PROPERTIES
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Questions:
- How do you explain this
patient hyperkaliemia?
- How would you manage it?
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- Describe the common drug
interactions involving
medications used to treat
atrial fibrillation?
- How can you prevent
them?
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Notes:
The patient finally improved and got extubated.
Unfortunately, because of his baseline psychosis,
it was impossible to obtain a history for the
present illness. The meningitis treatment was
completed and the patient was eventually
transferred to the Psychiatric Unit.
References
Boyer, E.W., Shannon, M. The serotonin syndrome. N Eng J Med. 352, 1112-1120
(2005).
Hadad, E., Weinbroum, A.A., Ben-Abraham, R. Drug-induced Hyperthermia and
Muscle Rigidity: a Practical Approach. Eur J Emer Med. 10, 149-154 (2003).
Jenkins, D.H. Substance Abuse and Withdrawal in the Intensive Care Unit. Surg Clin
N Am. 80 (3), 1033-1053 (2000).
Spriet, I., Meersseman, W., De Hoon, J., Von Winckelmann, S., Wilmer, A., Willems,
L. Mini-series II: Clinical Aspects. Clinically Relevant CYP450-mediated Drug
Interactions in the ICU. Intens Care Med. 35, 603-612 (2009).
Streetman, D.S. Metabolic Basis of Drug Interactions in the Intensive Care Unit. Crit
Care Nurs. 22 (4), 1-13 (2000).
Notes:
RCPSP OBJECTIVES:
7.5 Intoxication
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7.5.1
The ability to formulate a differential diagnosis for a patient potentially
suffering from a toxic syndrome and undertake a sequential plan to support organ function, prevent
further absorption, alter distribution, and if possible, enhance elimination by natural and mechanical means.
7.5.2 Demonstrate knowledge of:
7.5.2.1 the general support, together with any specific antidotes or supportive therapy pertinent to individual
intoxicants
7.5.2.2 the pharmacology of common intoxicants
7.5.2.3 strategies to reduce absorption and enhance elimination (hemodialysis, hemoperfusion)
7.5.2.4 the need of patients and families for emotional and psychiatric support
8.2 Pharmacotherapy
8.2.1
Have a thorough knowledge of indications, risks, and side effects of relevant pharmacotherapy.
8.2.2 Demonstrate knowledge of:
8.2.2.1 the principles of clinical pharmacology
8.2.2.2 the pharmacologic and therapeutic applications of drugs
8.2.2.3 side effects, drug interactions associated with medications
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