Abstract
Removal of serum toxins using haemofiltration with human albumin has
been demonstrated to be a useful option for the
treatment of a patient following the ingestion of unknown substance.
Here, a case is described in which a patient presented with
symptoms of neuroleptic malignant syndrome after ingesting an unknown
Nigerian herbal remedy. Albumin enhanced continuous
veno-venous haemodialysis has been previously used for intoxications.
When combining continuous renal replacement therapy
with albumin, the toxins are bound to the larger molecule which prevents
the toxins moving through the filter; allowing for clearance
from the blood. We suggest that Intensive Care Units should consider
basic tools, such as detox haemofiltration when an unknown
poison is suspected.
Introduction
Neuroleptic malignant syndrome (NMS) is a medical
emergency, made more difficult by the lack of any diagnostic
investigations, making it an entirely clinical diagnosis. Four criteria
are used as parameters for a likely diagnosis: a change in mental
status, a muscle rigidity (lead-pipe type), hyperthermia and signs
of autonomic instability. TOXBASE guidelines state that in cases
of suspected poisoning, activated charcoal may be used within
1 hour of ingestion; However, in cases like this where the patient
is late in presentation, options are more limited. To our current
knowledge, there is no specific antidote, and recommended therapy
is supportive only. A few case reports have suggested the use of
CVVH, peritoneal dialysis, and haemodialysis. In the absence of any
diagnostic tests, we felt it was prudent to initiate renal replacement
therapy in an attempt to filter any precipitating substances, without
waiting for the development of further symptoms. Here we discuss
the use of albumin enhanced continuous renal replacement therapy
to treat a likely neuroleptic malignant syndrome.
Case Report
A 60-year-old male presented to the Accident and Emergency
Department with reduced conscious level, diarrhoea and vomiting.
The patient had ingested an unknown powder sent from Nigeria
two days before presentation, for use as a treatment for his recently
diagnosed Hepatitis B infection. Other past medical history includes
type 2 diabetes mellitus, hypertension and hypercholesterolemia,
treated with metformin, gliclazide, ramipril and atorvastatin
respectively. The patient’s wife subsequently gave a collateral
history, explaining that the patient had taken the unknown substance
from Nigeria, knowing that it would make him very unwell for 3
days. She called for the ambulance on the 2nd day due to his reduced
conscious level and vomiting. Upon initial assessment, respiratory
rate was 35/min, heart rate 115/min, blood pressure 100/60mHg
and temperature of 39oC. On auscultation he had crackles at both
lung bases, a finding consistent with a chest x ray that demonstrated
bilateral infiltrates, suggestive of either bronchoaspiration or
pulmonary oedema. Cardiovascular and abdominal examinations
were otherwise unremarkable. On neurological examination, there
was severe lead pipe rigidity of all four limbs and neck stiffness
accompanying a Glasgow Coma Score (GCS) of 10 (E3 V2 M5), though
with normal pupillary reflexes. Arterial blood gas results were: pH
7.22 pCO2 7.11, pO2 14.4, Hb 132, Glucose 12.6, Lactate 1.6, Base
Excess- 4.9, HCO3 19.4. Abnormal blood tests included: Urea 15.8,
Creatinine 207, CK 1600, WCC 3.1 (neutrophils 2.1, lymphocytes
0.8), INR 1.4. CT Thorax abdomen and pelvis showed bilateral
patchy areas of consolidation, ground-glass opacities and air
space opacities suggestive of aspiration pneumonia. CT head was
normal. [1-4] ECG and bedside echocardiography were normal.
An uncomplicated intubation was performed due to hypercapnic
respiratory failure and reduced GCS, and the patient was transferred
to the intensive care unit. A nasogastric tube was inserted and
300ml of yellow-brown fluid was removed. The following antibiotic
treatment was commenced: co-amoxiclav, clarithromycin and
amikacin. High flow continuous veno-venous haemofiltration
in combination with IV human albumin was started to remove
potential precipitating agent. The patient improved quickly, and
the small dose of noradrenaline started on day 1 was weaned off
within 24 hours. The muscle rigidity improved slowly over 4 days
but became the primary issue, along with inappropriate waking
from sedation. A repeat CT head was performed which was normal,
and an EEG was also normal. The neurological symptoms improved
by day 5 and he was successfully extubated. He spent a subsequent
3 days on the unit until his pneumonia was fully resolved and was
discharged on day 9.
Methods
High volume veno-venous filtration was performed using an
Aquarius System. Blood was driven through a highly permeable
haemofilter type Aquamax HF 12 poly-ether-sulfone from Baxter
(cut-off point of 30.000 Dalton); systemic anticoagulation was
also added into the haemofilter and pre-dilution mode was used.
Extracorporeal blood flow ranged from 250 to 360ml/min (60ml/
Kg). The principle of clearance in this model of continuous dialysis
was convection. No fluid was taken from this patient to maintain
haemodynamic stability. The procedure was performed over the
course of 48h. Albumin 20%, 100ml, was administered three times
during the procedure due to the expectation that toxins would
bind to the albumin which has a high molecular weight and will
be trapped by the filter .Toxicology was contacted on admission;
Dantrolene was considered but not administered, as it was unclear
at the time whether this was a NMS; we were advised to use it only
if autonomic disturbances were present. A screening of > 1000
substances were tested in the National Laboratory of Toxicology
but non potential toxics were identified.
Discussion
According to the patient’s family, the substance which he
ingested was a soluble powder sent from Nigeria called “agumu”.
After researching this term, we have discovered this is a generic
name for “medicine” and has multiple different references, but not
1 specific treatment [5-8]. The substance was sent for toxicological
analysis at a national laboratory testing for 1500 different drugs
but was not flagged as positive for any of them. We performed a
literature search and found that there is a very limited amount
of information regarding Nigerian herbal remedies which fit the
description provided by the family of the patient. We were able to
identify 1 compound, Rauwolfia Vomitoria that has been used in
Nigerian herbal remedies for several purposes, and is known for
its anticonvulsant, analgesic and antipsychotic properties. This
compound has a similar effect profile as Chlorpromazine, which
is a dopamine antagonist, and can cause neuroleptic malignant
syndrome in overdose. Unfortunately, we did not discover the true
identity of the substance, so further speculation is not helpful.
However, the usefulness of the albumin haemofiltration may still
be discussed. Many antipsychotic medications are highly lipid
soluble and have high levels of protein binding. The above example
of chlorpromazine has a 90-99% protein binding capacity. In the
severely affected patients, it is theoretical that increasing serum
albumin levels would increase the bound fraction of the drug,
and therefore prevent the drug from moving through the filter.
On the other hand, it is not clear whether patients with a normal
endogenous serum albumin concentration would already have
sufficient levels of protein binding capacity. Due to the severity of
the case, the potential harm caused by line insertion and filtration
is likely outweighed by the potential benefit, as these patients often
end up on the filter due to renal failure secondary to either direct
drug nephrotoxicity or secondary effects from high creatinine
kinase levels.
Conclusion
Thankfully, this patient made a full recovery, and we have
counselled him regarding the ingestion of unknown substances
before discussion with a doctor. Due to many confounding factors
in this case, it is difficult to demonstrate causality with any single
intervention. However, these patients can prove to be challenging,
especially in the early stages of presentation where the history is
unclear. With the lack of diagnostic tests, and the inevitable delay
in serum drug sampling, it is reasonable to start therapies which
are likely to do little harm but may have a large positive impact. We
believe the albumin hemofiltration is such an example.
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