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Archive
Welcome! This
is the final gas problem in this series. Most of the case scenarios will have an emphasis on
Anaesthetic or Intensive Care practice but interesting gas results on
other patients that I come across may be included. Most of the results
are ones you could typically come across in your daily practice so the
emphasis is not on finding strange or extreme results though some
unusual results may be included. Perhaps you have come across an
'interesting gas' - please feel free to send this along to me at kbrandis@bigpond.net.au.
The style of analysis used here is that presented in my book
"Clinical Acid-Base pHysiology" (now available on-line).
Please consider the following clinical
scenario and then consider the question & discussions that follow.
Home | Gas Archive
History
A 47 year old man took an
overdose of colchicine 42mg, indomethacin 875mg and alcohol with
suicidal intent. He awoke the next morning (10 hours post-overdose) with
diarrhoea, vomiting and crampy abdominal pains. These had continued
since and he finally presented to hospital 36 hours post-overdose. The ambulance
notes record: "Resp -tachypnoea. Hyperventilation with
associated tingling in hands and lips". Arrived at hospital
0655hrs. He had a past history of depressive illness.
Examination
On admission: He was awake & talking. SpO2 97% on room air, pulse
80/min, BP 120/70, resp rate 20/min, heart sounds normal, chest clear,
peripheries cool. He was thirsty.
Management
He was admitted to the Intensive Care Unit. Management included volume
replacement with crystalloid, phosphate replacement, mannitol 20% and
frusemide 500mg.
Blood gases &
other Investigations
| Gas
No 6. |
0739
hrs |
0908
hrs |
1042
hrs |
1204 hrs |
1425 hrs |
Ref
Range & Units |
| FIO2 |
|
|
0.21 |
|
0.21 |
|
| pH |
|
|
7.57 |
|
7.57 |
|
| pCO2 |
|
|
17 |
|
25 |
mmHg |
| HCO3 |
|
|
16 |
|
24 |
mmol/l |
| pO2 |
|
|
109 |
|
87 |
mmHg |
| BE |
|
|
-2.8 |
|
3.3 |
mmol/l |
| Hb |
202 |
|
186 |
|
166 |
g/l |
| MetHb |
|
|
0.6 |
|
0.7 |
% |
| HbCO |
|
|
<0.2 |
|
<0.2 |
% |
| Na |
|
150 |
148 |
146 |
146 |
mmol/l |
| K |
|
2.8 |
2.7 |
3.2 |
3.2 |
mmol/l |
| Cl |
|
101 |
|
104 |
|
mmol/l |
| 'Bicarbonate' |
|
18 |
|
22 |
|
mmol/l |
| Anion gap |
|
31 |
|
20 |
|
(4-13) mmol/l |
| Lactate |
|
|
10.3 |
|
3.5 |
(0.7-2.5) mmol/l |
| Urea |
|
11.0 |
|
10.3 |
|
(3.0-8.0) mmol/l |
| Creatinine |
|
0.26 |
|
0.17 |
|
(0.07-0.12) mmol/l |
| Osmolarity |
|
305 |
|
296 |
|
(270-290) mOsm/kg |
| Creatine kinase |
|
966 |
|
|
|
(< 200) U/l |
| cTroponin I |
|
0 |
|
|
|
(<0.7) ug/l |
| Albumin |
|
43 |
|
35 |
|
(33-47) g/l |
| Ionised Ca |
|
|
0.98 |
|
0.98 |
(1.15-1.35)
mmol/l |
| Mg |
|
0.49 |
|
0.36 |
|
(0.70-1.0)
mmol/l |
| Phosphate |
|
0.25 |
|
0.80 |
|
(0.70-1.40) mmol/l |
Other results:
* Platelet count fell from 331 (x109/l)
on admission to 35 (x109/l) three days later
* Moderate coagulopathy
Questions
[1] Are there any
acid-base disorders associated with a colchicine overdose?
[2] What does the first set of acid-base results show?
Consultant
(to Registrar)
Is a colchicine overdose a serious concern?
Registrar
Yes, its a major life-threatening event.
Many overdoses are of drugs that depress the CNS and these cause death
due to respiratory depression and airway obstruction. In such situations
then, once the patient reaches hospital in reasonable condition survival is
highly likely
(>99% survival). This is because airway protection and ventilatory
support is so easy to do in an Intensive Care setting. Monitoring and support of the cardiovascular system is
also well established
and mostly efficacious.
But a colchicine overdose is much more insidious and patients can die
despite reaching hospital alive (as in
this
other case report). Acid-base disorders though are not usually a major
part of the clinical picture in the earliest stage. Colchicine is a
cytotoxin because it is a micro-tubule disrupting alkaloid.
Consultant
Are there any particular acid-base
disturbances that occur with a colchicine overdose?
Registrar
There is no specific disorder due to the colchicine in the same way that
phenformin, for example, is associated with lactic acidosis. Many such
patients have been reported to develop acid-base disorders due to the
consequent effects of the overdose. For example, possibilities include:
* vomiting -> metabolic alkalosis
* diarrhoea -> hyperchloraemic (or normal anion gap) metabolic
acidosis
* volume depletion -> lactic acidosis due to poor peripheral
perfusion
* muscle weakness (eg due to the electrolyte disorders) could result in
respiratory failure with respiratory acidosis
* cardiac arrest -> lactic acidosis & respiratory acidosis
The best approach is to be aware of a range of possible disorders and
assess the patient using the standard gamut of history, examination and
investigations.
A metabolic acidosis is the most
likely acid-base disorder and this may develop after admission. This is
not a static situation as the toxicity due to colchicine develops over a
few days.
Consultant
You mention vomiting as causing metabolic alkalosis, but don't you think
that in general terms this is unlikely in this particular overdose
situation?
Registrar
Protracted vomiting of acidic gastric contents results in a metabolic
alkalosis. This is one of the major causes of metabolic alkalosis.
Indeed just 2 causes (vomiting and diuretic use) account for about 90%
of cases.
So looking at this overdose situation then in the 'general terms' you
mentioned: For alkalosis to develop we must have:
* vomiting
* the vomitus must be acidic
* this must be of a sufficient severity (amount lost &
duration)
Well, the patient is vomiting. Gastric secretions are acidic. So, if the
vomiting continues then a metabolic alkalosis would develop. However, I
think I see your point: We have vomiting and it may last long enough but
what is the acid state of the vomitus lost? Gastric content will be
acidic UNLESS the patient is on anti-acid drug therapy (eg ranitidine)
or the patient has achlorhydria. Neither of these are present or likely
here (based on history) so I would expect that the gastric content is
indeed acidic in this patient.
But I think the significant thing is that
the vomitus is not just gastric juices but also secretions from the
duodenum and these are alkaline. So a person could be vomiting for say two
days but the vomitus could be a mixture of acidic secretions from the
stomach and alkaline secretions from the upper small intestine
(including bile) so they may not be a net acid loss and you won't get a
metabolic alkalosis. Or indeed maybe you could get a hyperchloraemic
acidosis in some circumstances (eg patient on H2-blocker). So the point
is that vomiting doesn't inevitably lead to metabolic alkalosis.
Thinking further along these lines: If the alkaline duodenal contents
were prevented from mixing with the gastric acidic secretions then
vomiting would much more predictably cause metabolic alkalosis. So
pyloric stenosis such as occurs in babies, or as occurs as a
complication of peptic ulcer disease in some adult patients would be a
more likely situation where vomiting would be much more likely to cause metabolic
alkalosis.
Consultant
You use the word 'cause'. Is this what you mean?
Registrar
I agree it needs some qualification when talking about metabolic
alkalosis. A metabolic alkalosis has to be considered in two
parts:
* How it is generated? ("the cause")
* How it is maintained?
The kidney under normal circumstances has a tremendous capacity to
excrete bicarbonate. Any rise in plasma bicarbonate due to 'the cause'
of the alkalosis will result in a rapid excretion of bicarbonate so any
metabolic alkalosis will tend to be mild and rapidly corrected.
So, vomiting, especially with pyloric stenosis, will generate or 'cause'
only a transient or mild metabolic alkalosis unless the kidney's ability
to excrete the bicarbonate is severely diminished. For a metabolic
alkalosis we need two things: something to generate it and something
else to maintain it. This second thing maintains the alkalosis by
interfering with bicarbonate excretion by the kidney.
Consultant
What is the most important abnormality that maintains a metabolic
alkalosis?
Registrar
The commonest situation is chloride depletion. In simple terms, if there
is a shortage of this anion, then the kidney's tubular function is
altered such that the next most common anion present (bicarbonate) is
much more avidly retained. Vomiting of gastric content then is ideally
suited to cause the alkalosis (loss of H+) and also to set up the
situation which maintains the alkalosis (loss of chloride as the gastric
acid is HCl so there is an obligatory chloride loss).
This discussion has been an interesting sideline but I don't think that metabolic
alkalosis is particularly likely here. Possible but not likely. This is
a life-threatening overdose of colchicine and there are other issues of
much more importance to the patient's management.
Consultant
I take your point. Perhaps I have focussed on a much less likely
possibility.
Well then, perhaps you can orient me in the right direction with a brief
overview of what is likely with a colchicine overdose, and then we can
focus on the acid-base situation in this particular patient.
Registrar
A brief overview of colchicine overdose then:
Latent period
There is a period after the overdose where there are no symptoms due to
the colchicine.
This latent period may be 2 to 12 hours.
First phase: The GI phase
The patient develops nausea, vomiting, abdominal pains and diarrhoea.
These are not in themselves life-threatening but should result in the
patient coming to medical attention. The potentially serious nature of
the overdose must be recognised and the patient must be admitted to
hospital.
Second phase: Widespread organ toxicity
This occurs 1 to 3 days after the overdose. Toxicity affects many organs
and may include respiratory depression, respiratory muscle weakness,
pulmonary oedema, myocardial depression, volume depletion due to
extensive loss of intravascular fluid to the tissues and also due to
vomiting, consequent hypotension and shock, neurological toxicity
resulting in confusion or coma, paralytic ileus, haematological problems
with coagulation disorders, thrombocytopaenia, granulocytopaenia, renal
failure (prerenal or renal) with oliguria & azotaemia, myoglobinuria,
electrolyte disturbances (esp hypokalaemia, hyponatraemia,
hypocalcaemia, hypophosphataemia) and metabolic acidosis.
Third phase: Recovery phase
Patients who survive will slowly recover. Alopecia is an event which has
been reported as developing a week or
more after a colchicine overdose. This does not represent new toxicity so does
not require any new intervention.
Consultant
Good, I think you have given a good concise overview. This patient certainly developed serious electrolyte disturbances
and a severe thrombocytopaenia. Now, what do you think of the initial
set of blood gas results?
Registrar
This initial set of gases were done about 3.5 hours after arrival at the
hospital. My initial 3-point scan of the results shows an alkalaemia, hyperventilation and
adequate oxygenation (on room air). Going through the results
systematically then in the usual way:
1. pH: At 7.57 there is a significant alkalaemia present so
there is an underlying alkalosis present.
2.
Pattern (of pCO2 & HCO3- results):
The pCO2 & the HCO3- are both decreased. This
pattern suggests a respiratory alkalosis or a metabolic acidosis:
| * |
In a respiratory alkalosis, the decrease in the pCO2 is the primary
event and the decrease in HCO3- is the
compensatory event.
|
| * |
In a metabolic acidosis, the decrease in bicarbonate is the primary
event and the decrease in pCO2 is the compensatory event.
|
In this case then, the
pH is 7.57 so it is known that an alkalosis is present so the choice is
easy: there is a respiratory alkalosis present.
3.
Clues: The electrolyte results from an hour and a half
earlier show a decreased bicarbonate with an Anion Gap of 31
(=150-101-18). An anion gap this high invariably means a metabolic
acidosis is present. The measured lactate level is 10.3 so there is a
severe lactic acidosis.
4.
Compensation: The expected compensation for an acute
respiratory alkalosis is determined using Rule 3: The bicarbonate will
decrease by 2 mmol/l for every 10mmHg decrease in arterial pCO2
below 40mmHg. So here we would expect a bicarbonate level of 19 to
20mmol/l. The actual level is 16 which provides support for the presence
of a co-existing metabolic acidosis.
5.
Formulation: My acid-base diagnosis is that a mixed disorder
is present: A respiratory alkalosis and a metabolic acidosis (lactic
acidosis).
6.
Confirmation: No specific confirmatory tests are required.
Consultant
So what is your overall clinical diagnosis?
Registrar
Serious colchicine overdose with multi-organ toxicity including a lactic
acidosis and hyperventilation causing a respiratory alkalosis. The
hyperventilation was noted clinically and reflects both the ventilatory
response to the metabolic acidosis and the distress from the abdominal
pain. The lactic acidosis probably reflects impaired perfusion and the
tissue toxicity from the drug. The elevated [Hb] means loss of fluid
from the intravascular compartment and this hypovolaemia would be
associated with impaired tissue perfusion. The presence of serious
electrolyte abnormalities is also noted, particularly the low Mg++
and phosphate levels.
Consultant
Would it help if this patient had been commenced
on haemodialysis soon after admission?
Registrar
No. Colchicine is a lipophilic alkaloid with consequent rapid absorption
and large volume of distribution. This means that haemodialysis is not
useful for removing the drug. Specific therapy with colchicine specific
antibody fragments has been reported but I don't know if this is
available in Australia. Otherwise treatment is generally supportive care
in an Intensive Care Unit. Cardiac toxicity with cardiac arrest
may result in a fatal outcome despite treatment. A high urine output
should be maintained to prevent damage from myoglobinuria consequent on
muscle injury. The cardiac depression and the volume depletion are other
reasons for volume loading of these patients.
Consultant
This patient survived. The documented dose of 42mg is interesting as
studies have shown survival in adults is usual with doses less than 40mg
but unlikely with doses in excess of 50mg. Another study found survival
with doses <0.5mg/kg but death with doses >0.8mg/kg. A few more
tablets and this patient may have died. Sometimes substantial toxicity
has been reported with much smaller doses.
We have not commented
on the co-ingestion of indomethacin here. This itself may result in
significant toxicity. Indocid & colchicine compete for transport in kidneys.
Finally, colchicine inhibits the action of ADH in the kidney and this
presumably reflects the role of microtubules in the vesicular
trafficking of aquaporin 2.
The above is a
purely hypothetical dialogue which is presented for educational
purposes.
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