ILEUS STATES – CONDITIONS CONNECTING PSYCHIATRISTS AND SURGEONS?

Background. Ileus states are serious conditions that may lead to pathophysiological changes which in turn can result in perforation of bowel, peritonitis, sepsis or death. Our paper discusses paralytic ileus states, which can be caused by psychopharmaceutics with anticholinergic side effects. Methods and Results. Retrospective analysis of cases of paralytic ileus in mentally ill patients admitted to Mental Hospital Kromeriz. Conclusion. Although some old psychopharmacs have a much higher potential for anticholinergic side effects than the new ones, there are still some of the new modern antipsychotics which also have anticholinergic side effects which could cause paralytic ileus. Both psychiatrists and surgeons should pay attention to atypical or changed signs of ileus states in mentally ill patients and should be aware of the confounding factors which could make the diagnosis of ileus difficult in mentally ill patients.


INTRODUCTION
Ileus states form an important group of conditions that rank amongst causes of acute abdominal pain.The term Ileus means that the passage of stool through the bowels is stopped.Ileus is a serious pathology that can occur at any time from childhood, with increasing prevalence in older patients.Ileus represents about 20% of cases of acute abdominal pain.Ileus states can be classified according to many factors: (A) acuteness and chronology of its development, (B) completeness of blockage, (C) fac-tors causing ileus states, (D) localization of blockage in passage of stool [1][2][3] (Table 1).
Ileus states can be characterised by a quick development of changes in the body 1,4,5 .In the case of mechanical ileus, there can be seen a distension of bowel above its blockage.This distension is as a result of the congestion of fluid and bowel gas above the point of bowel blockage.Fluid collected in distended bowel means potentially significant leakage of water and minerals out of blood vessels.This is routinely termed leakage into the "third space".Hence, this redistribution of intravascular water   In addition, the rupture of overdistended bowel and peritonitis or sepsis can be fatal complications of ileus [2][3][6][7][8] .

Typical clinical signs of ileus states
Clinical signs of ileus states can change dynamically in time -as they may also change in the case of all other causes of acute abdominal pain 2,3 .
(1) Abdominal pain can be a leading symptom of ileus.There may be constant abdominal pain localized first above the blocked part of bowel.This pain can spread to become diffuse abdominal pain (signifying the rupture of bowel and peritonitis).
(2) Nausea and vomitus, which can be caused either by reflexive or compensatory mechanism.
(3) Blockage of passage of stool and gas per vias naturales -no stool and gas passes through the bowel (exceptionally there can be "false" passage of stool and gas in case of high ileus, when the bowel is intact and can transport stool and gas).Physical examination of the abdomen is an indispensable part of diagnosing ileus (inspection, palpation, percussion, auscultation of all the abdominal surface, including per rectum examination) as well as laboratory check (RBC, WBC, minerals, osmolality, glycaemia, urea, creatinin, liver enzymes markers, urine check), horizontal roentgen scan of the abdomen (with detection of typical hydroaeric phenomena), ultrasonography of abdomen (can be helpful in detection of blockage in the bowel, distension of bowel above the blockage, fluid in abdomen) or computerized tomography of the abdomen 1-3 (Table 2).

Prevalence of ileus states is higher in patients taking some sorts of psychopharmaceuticals compared to general population
The prevalence of ileus states appears to be higher in patients taking some sorts of psychopharmacs, in comparison to the general population.All psychopharmacs with anticholinergic side effects can lead to changes in mobility of bowel and result in paralytic ileus 9 .Paralytic ileus associated with anticholinergic side effects of some older antidepressants (such as amitryptiline, clomipramine, imipramine), first generation antipsychotics (such as chlopromazine, thioridazine, flupenthixol) and hypothetically in some cases of mood stabilizers , has been described 10-14,15-20 .
After treatment with antipsychotics, histological changes in structure of intestine were described in animal models.These changes are suggestive of inflammation, oedema and hemorrhage 21 .
Generally, the era of new modern psychopharmacs brought less side effects for patients treated by the new generation of antidepressants or antipsychotics, resulting in better adherence and better quality of life of mentally ill patients.On the other hand, some of the side effects remained due to the receptors involved and pharmacodynamics of the new psychotropic drugs..Even in case of recent generations of antidepressants or antipsychotics of the second generation we should be aware of the potential anticholinergic side effects, leading clinically to dysuria, retention of urine, visual disturbances (changes in accommodation, dryness of sclera), confusional states, gynaecologica conditions (dryness of vaginal and other mucous membranes) or paralytic ileus 4,9 (Table 3).

Uncertainty about clinical signs in cases of patients with psychiatric morbidity
This atypical clinical picture can be typically found.This should encourage all clinicians to be aware (especially in cases of absence of typical clinical signs of ileus states) of therapy or other pathological conditions which may change these typical diagnostic signs.
Patients suffering from mental disorders provide an example of a situation in which typical clinical signs can be masked, altered or absent .Psychopharmacs may change or lower the threshold of perceiving pain, which may lead Table 3. Psychopharmacs that may cause anticholinergic side effects leading to paralytic Ileus.
(A) Antidepressants -tricyclic antidepressants (such as amitriptyline, clomipramine, imipramine…) -heterocyclic antidepressants (such as trazodone, nefazodone) -selective serotonin reuptake inhibitors (rarely, fluoxetine could be mentionned here) -dualistic antidepressants (mirtazapine has some anticholinergic effects) (B) Antipsychotics -first generation of antipsychotics (FGA) (such as chlorpromazine, thioridazine, flupenthixol, haloperidol and many others) -second generation of antipsychotics (SGA) (such as clozapine or olanzapine) ( C) Mood stabilizers -lithium 19 , carbamazepine 20 (in toxic dosage?)Ileus states -Conditions connecting psychiatrists and surgeons?to loss of sensitivity towards pain or altered perception of pain.Patients with mental disorder (especially those with a lifelong course and having a defect in intellect) may ignore symptoms of pain or assume they are part of the condition.Furthermore, sometimes there is a risk of misintreptreting one can interprete abdominal pain as a symptom of basic mental disease (especially in case of paranoid states, somatoform states, hypochondriac states, personality disorders with associated hypersensitivity, factitious disorder or simulation) 10,12 .
Both psychiatrists and surgeons should take into account other factors as mentioned above in mentally ill people which sometimes make diagnosis and differential diagnosis of ileus states extremely difficult (Table 4).

Case 1
47 years old female pensioner, 12th hospitalization in Mental hospital in Kromeriz.Treated for paranoid schizophrenia since 1982 with long term course and experiencing residual symptoms (paranoia and cognitive impairment).Psychopharmacological history: chlorpromazine, thioridazine, diazepam, amitriptyline.Actual pharmacotherapy: levomepromazine 200 mg daily, clozapine 400 mg daily (dosage increased gradually during this hospitalization from 300 mg daily), clonazepam 1.5 mg daily.
On the 15th day of hospitalization, she develops anorexia with abdominal distension and conbstipation.Conservative treatment of constipation fails, on the 16th day of hospitalization patient suffers from diffuse abdominal pain with rapid progression to paralytic ileus.Surgical revision including laparotomy was vital, with findings of low ileus of thin bowel.

Case 2
56 years old, male pensioner, 8th hospitalization in Mental hospital in Kromeriz.Treated for residual schizophrenia and hypertension.First symptoms appeared in 1978.Admitted to hospital because of relapse of imperative auditive hallucinations.Psychopharmacological history: chlorpromazine, chlorprothixene, thioridazine, lithium, valproate, benzodiazepines.Actual pharma-cotherapy: antihypertensives (betaxolol 10 mg daily -betablocker), clozapine 500 mg daily, flufenazine in depot galenic form (25 mg each 3 weeks).Dosage of any psychopharmacs used in actual therapy has not been changed.
29th day of hospitalization patient complains of nausea, vomiting, atypical sensation localized in lower abdomen.Auscultation of abdomen shows no signs of bowel peristalsis.X -ray scan of abdomen by horizontal X-ray show dilatation of caecum and hydroaeric phenomena with caecal localization.Surgical intervention including laparotomy and revision of abdomen was required.
25th day of hospitalization nausea and constipation appear together with umbilical abdominal pain, surgical liaison service was required and made a diagnosis of low ileus in bowel.Patient was treated conservatively -conservative treatement included parasympatholytics, rehydratation, dietary provision and watchful observation.Regression of paralytic ileus was observed then, with no need of surgical revision.

CONCLUSION
We bring three case reports of patients treated for paranoid schizophrenia, residual schizophrenia and schizoaffective disorder-depressive type.Their actual medications (including mostly antipsychotics of first generation) could have anticholinergic side effects, clinically leading to development of ileus states requiring consultation and therapy by surgeon.Polypragmasis was evident in all cases, this can be an important confounding factor.
Many patients suffering from mental disorders (especially with long term course of mental disease) are still treated with older generations of psychopharmacs which were used for treating them in former hospitalizations.Psychiatrists do not usually discontinue this medication especially if basic psychopathology is under control.We would like to provoke further clinically important questions: Should we change therapy with preference for new generation psychopharmacs in patients with chronic mental illness (especially if they are stabilized for their psychopathology with older forms of psychopharmacological medication)?Should we undergo this if at risk of relapse of mental disease?Or should we try to change therapy of our patients for more comfortable options, with less side effects including anticholinergic side effects and the perspective of better adherence?Any psychiatrist should be aware of pharmacodynamics of psychopharmacs which have been prescribed, including having a good knowledge of side effects of this medication.Antichollinergic side effects are one of the most important side effects, usually detected in older types of psychopharmacs which are still prescribed.
Both the knowledge of clinical symptoms of ileus states as well as its early detection and interdisciplinary collaboration with surgeons, can be vital in the care of mentally ill patients who develop ileus due to their therapy.

.
Classification of ileus states.
-neurogenous ileus (paralytic and spastic) -vascular ileus (caused by thrombosis or embolia in a vessel of the bowel wall) (D) Localization of blockage in passage of stool -high ileus of thin bowel -low ileus of thin bowel -ileus of large bowel Translated and modified to Ševčík et al.

Table 4 .
What can make diagnosis of ileus states difficult in mentally ill patients.