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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.

Gas Analysis No. 6 

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.

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.

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)
Mg   0.49   0.36   (0.70-1.0)
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


[1] Are there any acid-base disorders associated with a colchicine overdose?
[2] What does the first set of acid-base results show?

Theatre Discussion

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 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. 

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, 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. 

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:
* 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. 

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 management.

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:

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. 

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. 

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.

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

Last updated Sunday, 04 August 2002 12:53 PM EST

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