Multimodal prospective analysis and definition of biomarkers for the improvement to predict Critical-Illness-Polyneuromyopathy (CRIT-PATH)

Status:

completed 08/2020

Aims:

Critical illness polyneuromyopathy (CINM) or ICU-acquired weakness (ICUAW) is a common sequela of modern intensive care (ICU) worsening the prognosis during and after ICU. CINM can manifest as muscle weakness or neuropathy-like symptoms. Until now, only short-term disease progress has been investigated, and the diagnosis remains challenging. The aim of the current study was to investigate the long-term incidence of CINM, characterization and persistence of associated symptoms as well as the influence on quality of life (QoL) and to investigate various clinical and neurophysiological abnormalities in long-term survivors up to a decade post-ICU in comparison to controls.

Activities/Methods:

After ethical approval and registration, all patients (n=3647) admitted to an ICU in 2007–2017 in the BG-University Hospital were screened. Out of 1,860 patients 1,268 survivors were contacted. 149 patients gave informed consent and were interviewed regarding demographic data, medical history, comorbidities and occurrence, localization, onset, duration, recovery and consequences. CINM was considered as at least one proximal-symmetrical symptom of muscle weakness and/or a distal-symmetrical symptom of paresthesia, hypoesthesia, or (neuropathic) pain, without potential association with another disease occurring for the first time after ICU treatment. Further on, 28 critical care long-term survivors (recruited within the telephone interview) and 19 controls (recruited by advertisement; exclusion criteria: any ICU treatment, comorbidity causing polyneuropathy or myopathy) were investigated. Subjects were asked about their QoL (VAS, 0-100) and underwent a neurological examination and multimodal assessment of CINM-related functional and morphological changes using electroneurography (ENG), electromyography (EMG), quantitative sensory testing (DFNS protocol), skin biopsy and corneal confocal microscopy (CCM).

Results:

149 former patients (age: 63.5±13.1y; males: 73%; time post-ICU: 4.4±2.7y, 5-10y: 43%) responded to be interviewed. On average, patients (59.5±13.4y at ICU-admission) had spent 20.8±15.7d in the ICU with 396±328.8h ventilation. A CINM incidence of 74% (n=95/128, myopathy-like muscle weakness: 43%; neuropathy-like symptoms: 13%; mixed: 44%) was assessed. However, only 18% of participants had received an CINM diagnosis by their physicians, although 62% had persistent symptoms up to 10y after ICU (5-10y: 46%). Only 37% of participants reported a complete recovery of symptoms, significantly associated with an initially low number of symptoms after ICU (p<0.0001), only myopathy-like symptoms (p=0.024), and younger age at the time of ICU admission (55.7±13.1 vs. 62.6±10.6y, p<0.001). CINM still impaired the QoL at the time of the interview in 74% of affected survivors, with 30% reporting severe impairment. At the time of examination 28 patients (age: 60.5±14.9y, males: 82%, post-ICU: 3.75y ± 3.35; ICU-stay: 24.5±20.3d, ventilation duration: 371.7±354.6h) reported ongoing pain in 21% (intensity NRS 2.7±2.6), paresthesia in 50%, hypoesthesia 43% and muscle weakness 39%. Abnormalities were found most frequently in the clinical examination (82% of n=27) and in skin biopsies (89% from n=26), whereas CCM (32% from n=25) had the lowest sensitivity to detect abnormal values. Based on ENG and EMG, only half of the patients presented abnormalities indicating a CINM (ENG: 52% of n=27; EMG: 52% of n=21). Sensory loss was found in 17%. Only one patient showed no signs of CINM. 13 (48%) had a sensorimotor large fiber neuropathy, 10 (37%) had a sensorimotor-mixed polyneuropathy of the large and small nerve fibers and only three (11%) had a pure small-fiber neuropathy. In contrast, controls (age: 54,1±13,7y, males: 79%) showed no pathologies. Former ICU-patients reported lower hand grip strength (right: 31.2±12.1 vs. 42.3±11.5kg; p=0.003) and a lower QoL than controls even years after discharge (68.8±21.8 vs. 86.3±6.7 VAS; p=0.002).

The combination of symptoms, clinical examination and neurophysiological diagnostics can serve as a biomarker of the CINM. In particular, symptom anamnesis and force measurement with a hand dynamometer seem to be suitable as easy short- and long-term marker.

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