Correlates of new onset peripheral nerve injury in comatose psychotropic drug overdose patients.

AIMS: To investigate the relationship between the duration of comatose state, severity of rhabdomyolysis and frequency of peripheral nerve injury (PNI) in patients following psychotropic drug overdose.
MATERIALS AND METHODS: Medical charts were retrospectively reviewed for 41 patients admitted for disturbance of consciousness induced by an overdose of psychotropic drugs with rhabdomyolysis between October 2004 and February 2010. Subjects were divided into PNI group (n=9) and non-PNI control group (n=32).
RESULTS: Mean interval between drug ingestion and arrival, frequency of pressure ulcers, CK level at the time of patient's arrival and maximum CK level during hospitalization, duration of hospitalization and morbidity rate were all significantly higher in the PNI group than in the control group.
CONCLUSION: In patients with a psychotropic drug overdose leading to a comatose state, the longer the comatose state, the more likely that pressure ulcers and PNI will occur.

INTRODUCTION

Compartment syndrome involves injury to the nerves, vasculature and muscles by raised pressure within the compartment due to muscle injury, fracture, ischemia, or inflammation.[1-3] However, crush syndrome is characterized by major shock and renal failure following a skeletal muscle injury, as commonly seen with events such as earthquakes, where victims become trapped under collapsed buildings.[4] These two syndromes can also result in peripheral nerve injury (PNI) by direct compressive or traumatic nerve injury, or indirect injury from the raised pressure within the compartment.[1256] A patient in a comatose state induced iatrogenically or by drug overdose may also show complications of PNI due to compression of parts of body by the body itself following prolonged immobilization, resulting in the formation of a compartment or crush syndrome.[7-11] A longer duration of immobilization would thus seem likely to lead to more severe muscle injury,[12] following a more frequent occurrence of PNI in comatose patients following an overdose. However, few reports to date have examined this possibility. We therefore retrospectively investigated the relationship between duration of the comatose state, severity of rhabdomyolysis, and frequency of PNI in comatose patients following psychotropic drug overdose.

MATERIALS AND METHODS

Our institutional review board approved this study and waived the requirement for informed consent. During the investigation period between October 2004 and February 2010, a total of 199 patients were admitted for treatment following a psychotropic drug overdose, including 45 patients with rhabdomyolysis.

In this study, rhabdomyolysis was defined as present in a patient who showed creatinine kinase (CK) level on admission >160 IU/L, as the upper limit of normal as defined in our institution.

Two patients showing convulsions on arrival and two patients with neuroleptic malignant syndrome on arrival were excluded, as these conditions can also induce rhabdomyolysis. Medical charts were retrospectively reviewed for the 41 patients admitted with disturbance of consciousness induced by psychotropic drug overdose with rhabdomyolysis. These 41 patients were then subdivided into those with PNI (PNI group, n=9) and those without (control group, n=32). The presence of PNI was confirmed by the existence of extremity palsy or sensory disturbance after the patient regained consciousness. No PNI events were seen among the 158 patients who were excluded from analysis. Age, sex ratio, psychiatric diseases, physical data on arrival (Glasgow Coma Scale (GCS), systolic blood pressure, heart rate, and temperature), estimated interval between ingestion of the overdosed drugs and arrival, frequency of pressure ulcers (redness, swelling, or blister formation), CK level on arrival, duration of hospitalization, frequency of sequelae, and survival rate were all compared between the PNI and control groups. In the PNI group, the PNIs encountered, the drug overdosed, and estimated dose of each drug ingested were analyzed.

Statistical analyses were performed using Student's unpaired t-test and a χ2 analysis. Values of P<0.05 were considered as statistically significant.

RESULTS

Background data for the two groups are summarized in Table 1. Age, sex ratio, psychiatric diseases, and physical data on admission did not differ significantly between the two groups. The interval of time between drug ingestion, frequency of pressure ulcers and CK levels were all significantly higher in the PNI group than the control group. Figure 1 shows a scatter chart representing CK levels on admission. If the cut-off for CK level was set at 10,000 IU/L to predict the existence of PNI among patients in a coma due to drug overdose, sensitivity was 77.8% (7/9) and specificity was 93.8% (30/32).

Table 1

Background data for subjects

Figure 1

Scatter chart depicting creatinine kinase (CK) values on admission. If the cut - off point for CK was set at 10 000 IU/L to diagnose the presence of PNI among patients in a coma following drug overdose, sensitivity was 77.8% (7/9) and specificity was 93.8% (30/32)

CK level, PNIs identified, and treatments provided for the PNI group are shown in Table 2. The list of drugs overdosed by the PNI group is shown in Table 3. No trends were identified concerning specific PNIs. Two of nine patients who demonstrated sensory disturbances without paresis had symptoms that subsided within three months. However, while seven patients who demonstrated motor disturbances displayed improved paresis, none obtained complete recovery.

Table 2

List of peripheral nerve injury and values of creatinine kinase in the peripheral nerve injury (PNI) group

Table 3

List of ingested drugs in the peripheral nerve injury group

Table 4 shows the outcomes for the two groups. Duration of hospitalization was significantly longer and morbidity rate was significantly higher in the PNI group that in the control group.

Table 4

Outcomes for the two groups

DISCUSSION

The present results confirm that increased duration of comatose state is associated with increased risk of the development of both pressure ulcers and PNI.

In crush syndrome, significant correlations have been observed between the size of muscle injury and the duration of time trapped, peak serum CK level, and duration of hospitalization.[13] As expected, experimental studies suggest a dose-response curve in which greater duration and amount of pressure result in more significant neural dysfunction.[14] Among unconscious patients who were in a comatose state following a psychotropic drug overdose, a significant positive correlation has been found between the estimated interval between ingestion and admission and the CK level of admission to hospital.[15] In the present study, all patients in the PNI group experienced prolonged immobilization and showed pressure ulcers. Pressure ulcers also develop due to morphological and biochemical changes triggered by the combined effects of mechanical deformation, ischemia, and reperfusion that occur during extended periods of immobilization.[16] Accordingly, direct nerve compression or indirect nerve injury due to raised pressure in the body compartment containing the nerve during prolonged immobilization, resulted in the development of either paresis or sensory disturbances.

In terms of treatment for compartment syndrome, immediate fasciotomy is recommended when the compartment pressure exceeds 30 mmHg or when clinical symptoms are overt.[12] However, these recommendations were made based on clinical experience, and the level of evidence is still not definitive.[2] Conservative treatment has been reported to lead to functionally favorable outcome in at least some cases.[9] While, concerning the treatment of crush syndrome, Matsuoka et al. investigated peripheral nerve function two years after the 1995 Hanshin-Awaji earthquake in 42 patients with crush syndrome. That study found no evidence that fasciotomy had improved patient outcomes. Moreover, delayed rescue, delayed fasciotomy, and radical debridement may have worsened the physical prognosis. They therefore concluded that the indications for fasciotomy in crush syndrome during the acute phase require further deliberation, as suggested by Huang et al. when describing the Chi-Chi earthquake.[1718] The present study did not measure compartmental pressure except in one case, as all subjects in the PNI group had a delayed diagnosis of compartment or crush syndrome due to their unconscious state on arrival. The morbidity rate was significantly higher in the PNI group than in the control group. As evidenced-based guidelines concerning fasciotomy for the treatment of either compartment or crush syndrome are lacking, prospective randomized control studies are needed in the future to clarify the details of PNI among comatose patients following psychotropic drug overdose.

CONCLUSION

In patients with a psychotropic drug overdose leading to a comatose state, the longer the comatose state, the more likely that pressure ulcers and PNI will occur. In this study, patients with PNI, with paresis due to a comatose state following a psychotropic drug overdose, did not have a complete recovery.