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 firstname.lastname@example.org. The style of analysis
used here is that presented in my book "Clinical Acid-Base pHysiology" (now
Please consider the following clinical scenario and then
consider the question & discussions that follow.
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
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
He was admitted to the Intensive Care Unit. Management included volume replacement with
crystalloid, phosphate replacement, mannitol 20% and frusemide 500mg.
Blood gases & other
| Gas No 6.
|Ref Range & Units
|(< 200) U/l
* Platelet count fell from 331 (x109/l) on admission
to 35 (x109/l) three days later
* Moderate coagulopathy
 Are there any acid-base disorders
associated with a colchicine overdose?
 What does the first set of acid-base results show?
Consultant (to Registrar)
Is a colchicine overdose a serious concern?
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
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.
Are there any particular acid-base disturbances that occur
with a colchicine overdose?
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,
* 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.
You mention vomiting as causing metabolic alkalosis, but don't you think that in general
terms this is unlikely in this particular overdose situation?
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:
* 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
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.
You use the word 'cause'. Is this what you mean?
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.
What is the most important abnormality that maintains a metabolic alkalosis?
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
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.
A brief overview of colchicine overdose then:
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.
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?
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.
(of pCO2 & HCO3- results): The pCO2 &
the HCO3- are both decreased. This pattern suggests a respiratory
alkalosis or a metabolic acidosis:
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.
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
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.
My acid-base diagnosis is that a mixed disorder is present: A respiratory alkalosis and a
metabolic acidosis (lactic acidosis).
No specific confirmatory tests are required.
So what is your overall clinical diagnosis?
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.
Would it help if this patient had been commenced on
haemodialysis soon after admission?
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.
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.
Kerry Brandis, 2001