Intensive care unit acquired weakness in children: Critical illness polyneuropathy and myopathy

Background and Aims:

Intensive care unit acquired weakness (ICUAW) is a common occurrence in patients who are critically ill. It is most often due to critical illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is increasingly being recognized partly as a consequence of improved survival in patients with severe sepsis and multi-organ failure, partly related to commonly used agents such as steroids and muscle relaxants. There have been occasional reports of CIP and CIM in children, but little is known about their prevalence or clinical impact in the pediatric population. This review summarizes the current understanding of pathophysiology, clinical presentation, diagnosis and treatment of CIP and CIM in general with special reference to published literature in the pediatric age group.

Subjects and Methods:

Studies were identified through MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric studies were included.

Results:

ICUAW in children is a poorly described entity with unknown incidence, etiology and unclear long-term prognosis.

Conclusions:

Critical illness polyneuropathy and myopathy is relatively rare, but clinically significant sequelae of multifactorial origin affecting morbidity, length of intensive care unit (ICU) stay and possibly mortality in critically ill children admitted to pediatric ICU.     

Critical illness myopathy and polyneuropathy - A challenge for physiotherapists in the intensive care units

The development of critical patient related generalized neuromuscular weakness, referred to as critical illness polyneuropathy (CIP) and critical illness myopathy (CIM), is a major complication in patients admitted to intensive care units (ICU). Both CIP and CIM cause muscle weakness and paresis in critically ill patients during their ICU stay. Early mobilization or kinesiotherapy have shown muscle weakness reversion in critically ill patients providing faster return to function, reducing weaning time, and length of hospitalization. Exercises in the form of passive, active, and resisted forms have proved to improve strength and psychological well being. Clinical trials using neuromuscular electrical stimulation to increase muscle mass, muscle strength and improve blood circulation to the surrounding tissue have proved beneficial. The role of electrical stimulation is unproven as yet. Recent evidence indicates no difference between treated and untreated muscles. Future research is recommended to conduct clinical trials using neuromuscular electrical stimulation, exercises, and early mobilization as a treatment protocol in larger populations of patients in ICU.     

Diaphragmatic denervation in intensive care unit patients

The causes of prolonged requirement for mechanical ventilation in the intensive care unit (ICU) are currently a subject of investigation. Critical illness polyneuropathy (CIP), an axonal polyneuropathy that frequently occurs with prolonged sepsis and multi-organ failure, has been cited as a frequent cause of difficulty with weaning from a ventilator. The relative contribution of diaphragmatic denervation in ICU patients with and without CIP has not been definitively determined. We reviewed 102 ventilator dependent intensive care unit (ICU) patients. Critical illness polyneuropathy (CIP) was diagnosed based upon electrodiagnostic criteria. Electrodiagnostic studies included diaphragmatic needle electromyography (EMG) to evaluate for diaphragmatic denervation. The medical charts of the patients with diaphragmatic denervation were reviewed for etiologies other than CIP for the diaphragmatic denervation. Our results suggest: 1) Respiratory impairment in ICU patients may often be unrelated to either CIP or diaphragmatic denervation; 2) Only about half of ventilator dependent CIP patients have diaphragmatic denervation; 3) Diaphragmatic denervation in ICU patients frequently may be attributable to causes other than CIP.     

多脏器功能障碍患者胃肠功能衰竭中药治疗的研究

目的探讨中药治疗对多脏器功能障碍（MODS）患者胃肠功能衰竭改善的影响。方法回顾分析121例危重病患者在治疗过程中,合并胃肠功能衰竭时加用中药组（治疗组,68例）与未加中药组（对照组,53例）。比较两组胃肠功能衰竭的缓解率、缓解时间及MODS的发生率、病死率、ICU住院时间等。结果治疗组胃肠功能衰竭的缓解率明显高于对照组（75.0%vs55.7%,P=0.027）;治疗组比对照组胃肠功能衰竭的持续时间明显缩短[（2.52±2.10）dvs（10.85±3.85）d,P=0.00]、MODS的发生率明显减少（13.2%vs24.5%,P=0.027）、平均ICU住院时间明显缩短[（4.60±3.63）dvs（15.92±3.9）d,P=0.00];治疗组病死率与对照组比较差异无统计学意义（19.1%vs20.8%,P=0.741）。结论中药治疗结合常规治疗对危重病患者胃肠功能衰竭具有较好的治疗作用,可明显降低MODS的发生率、ICU住院时间,但对病死率无明显影响。     

Intensive Care Unit-acquired Weakness: A Frequent but Under-recognized Threat

How to cite this article: Sapra H. Intensive Care Unit-acquiredWeakness: A Frequent but Under-recognized Threat. Indian J Crit Care Med 2021;25(9):969–971.

Advances in modern medicine have been quite successful in reducing intensive care unit (ICU) mortality but post-ICU morbidity and impaired quality of life continue to be major concerns. Neuromuscular weakness developed in the critical illness survivors is one of the leading causes of incomplete functional recovery and persistent disability. In this issue of the journal, Baby et al. have published a prospective analysis of incidence, clinical course, and outcome of ICU-acquired neuromuscular weakness.¹ICU-acquired weakness (ICUAW) is a syndrome of generalized weakness defined as, “clinically detected weakness in critically ill patients in whom there is no plausible etiology other than critical illness.”² It is usually present beyond the first week of ICU stay with a reported incidence of >25%, which increases significantly in patients with sepsis (>60%).³ICUAW is classified into critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and critical illness neuromyopathy (CINM). The pathophysiological pathway is incompletely understood but may involve micro- or macrocirculatory impairment; bioenergetics failure; sodium channel inactivation; neurotoxins, like lipopolysaccharide and interleukins; hyperglycemia-induced oxidative stress; muscular atrophy; and mitochondrial or contractile protein dysfunction. The diagnosis can be made based on clinical features, neurophysiological testing, or nerve and muscle biopsy. It is characterized by generalized, symmetrical weakness including respiratory muscles and sparing cranial nerves, developing after critical illness onset with medical research council grade <4 in all testable muscle groups and distal sensory loss in CIP. Muscle wasting is usually variable and difficult to assess in the presence of edema. Neurophysiological testing includes nerve conduction studies determining nerve conduction velocities, compound motor action potentials (CMAP), sensory nerve action potentials (SNAP), and electromyography (EMG). CIP is characterized by reduced CMAP and SNAP with normal or near normal nerve conduction velocities. CIM is characterized by short duration, low-amplitude motor unit potentials on EMG, reduced CMAP on direct muscle stimulation, and muscle biopsy showing atrophy with thick filament loss or necrosis. Muscle biopsy further classifies CIM into three subtypes: cachectic myopathy, thick filament myopathy, and necrotizing myopathy. CIM patients have a better prognosis in terms of recovery than CIP. CINM will demonstrate overlapping features of both CIP and CIM. Baum et al. identified four different clusters of electrophysiological impairments, which can be useful for further categorization of severity and prognostication.⁴ The differential diagnosis may include conditions like Guillain–Barre syndrome, Myasthenia gravis, spinal cord injury, metabolic neuropathies, and toxic neuropathies. These can be ruled out based on the timing of onset of weakness in relation to critical illness and presence or absence of cranial nerves or extraocular muscles involvement.Recently, qualitative assessment of muscles with ultrasonography (USG) has been successfully used for the early detection of ICUAW. Other several techniques, such as computed tomography, magnetic resonance imaging, dual-energy X-ray absorptiometry, and neutron activation analysis, have also been used with more accuracy but these are time consuming, expensive, and associated with radiation exposure. Bioimpedance spectroscopy is another useful technique but its accuracy is limited by skin temperature, edema, or body position.⁵ Respiratory muscle strength can also be assessed for early detection of ICUAW. Maximum inspiratory pressure can be used as a surrogate parameter for early diagnosis of ICUAW.⁶ USG-guided evaluation of diaphragmatic excursion and diaphragmatic thickening fraction can be used to predict weaning outcomes.⁷ICUAW has several non-modifiable risks factors, like age, female gender, and severity of illness [Acute Physiology And Chronic Health Evaluation (APACHE) II score >15], and modifiable risk factors, like dyselectrolytemia, hyperglycemia, hyperosmolarity, mechanical ventilation (MV), parental nutrition, drugs like neuromuscular blockers (NMBs), amikacin, steroids, and vasopressors. Initial studies have shown a higher risk of ICUAW with older age; however, a recent meta-analysis did not find any significant association between age and ICUAW.^8,9 In this study, the mean age of patients developing ICUAW was 62.64 ± 14.4 years. Less muscle mass in females explains the higher susceptibility to develop ICUAW compared to males. Recent studies have shown a higher incidence of ICUAW with longer exposure to MV due to induced diaphragmatic weakness,³ but it is difficult to determine if prolonged MV leads to ICUAW or ICUAW increases the duration of MV. In this study, the mean duration of MV for patients developing ICAW was 9.27 ± 5.28 days compared to 3.87 ± 3.65 days in non-ICUAW patients. The association between corticosteroids and ICUAW is uncertain,^9,10 but their anti-inflammatory effect can exert some protective effect if hyperglycemia occurring secondary with their use is avoided with intensive insulin therapy.¹¹ NMBs promote ICUAW by aggravating the muscle weakness especially when administered for >48 hours or coadministered with steroids.¹² Routine use of such drugs should be avoided, especially when coadministered, and their indications, dosage, and duration should be regularly reviewed.The short-term consequences include prolonged MV, extubation failure, re-intubation, prolonged ICU stay, and increased cost. Long-term consequences include late death and reduced physical quality of life even 5 years after ICU discharge. In this study, the number of ICU days for patients with ICUAW was more than double and MV duration was three times higher than those who did not develop ICUAW. ICU mortality was also significantly higher in patients with ICUAW. In a study by Hermans et al., ICU and hospital mortality were not different but 1-year mortality was increased by 13% in patients with ICUAW.¹³ The likelihood of 1-year mortality was even higher with persisting weakness or increased severity of weakness after ICU discharge.Till date, no intervention has been proven to improve the outcome in ICUAW. Various preventive measures minimizing the risk factors have been used to reduce the prevalence of ICUAW. Hermans et al. in the secondary analysis of randomized controlled trials (RCTs) found that intensive insulin therapy (target blood glucose 4.5–6.0 mmol/L) reduces the incidence of ICUAW, duration of MV and ICU stay, and 180-day mortality.¹⁴ However, this was associated with a significant increase in life-threatening hypoglycemia. The current practice supports more liberal blood sugar control (target blood glucose 6.0–10.0 mmol/L) in critically ill patients. An RCT showed the positive effect of neuromuscular stimulation applied to limb muscles in improving walking distance and muscle strength in mechanically ventilated patients.¹⁵ Electrical muscle stimulation may also promote skeletal muscle growth and improve skeletal muscle microcirculation thus exerting a positive effect on tissue healing and prevention of bedsores. Limiting bed rest or inactivity with early mobilization and active or passive exercises can improve muscle function and reduce complications, like muscle shortening, contracture, and deformities. Schweickert et al. assessed the efficacy of early physical and occupational therapy along with daily interruption of sedation in mechanically ventilated patients.¹⁶ This strategy resulted in better functional status at hospital discharge and more ventilator-free days in the ICU. Therapeutic exercises should begin as soon as patients are hemodynamically stable; however, safety during mobilization should be assured to avoid falls, hemodynamic disturbances, desaturation, or accidental removal of medical lines.ICUAW continues to be an important healthcare concern in critically ill patients. It is associated with increased mortality and functional dependency in ICU survivors. Though exact prevalence is not known due to different diagnostic criteria, timing of assessment, and heterogeneous patient population, the incidence does not seem to be reducing with time. In the absence of any effective therapy, timely implemented preventive measured and early diagnosis should be the aim to improve the functional outcome in patients with ICUAW. Prolonged use of NMB with deep sedation should be avoided. Corticosteroids can be used especially in the treatment of refractory shock with adequate glycemic control. Early and aggressive measures to treat sepsis and maintain electrolyte balance and early institution of enteral nutrition along with a frequent review of medications can help in reducing the incidence of ICUAW. Manual muscle testing should be done at regular intervals in all cooperative patients to determine muscle strength. For unconscious or uncooperative patients, USG-guided qualitative muscle and diaphragmatic assessment is an inexpensive, bedside, and promising technique for early detection of muscle mass loss and ICUAW. Early institution of physical therapy in ICU is safe and feasible and should be started as soon as the patient is hemodynamically stable.In this study, Baby et al. have evaluated various patient factors and critical illness severity and correlated them with outcome parameters, including ICU days, MV days, and mortality. The higher age and APACHE score on ICU admission were associated with significantly higher ICU days, MV days, and mortality. More research work is required to establish therapeutic targets in the pathological pathway and to explore rehabilitation strategies starting within the ICU.     

Weak by the machines: muscle motor protein dysfunction – a side effect of intensive care unit treatment

Intensive care interventions involve periods of mechanical ventilation, sedation and complete mechanical silencing of patients. Critical illness myopathy (CIM) is an ICU‐acquired myopathy that is associated with limb muscle weakness, muscle atrophy, electrical silencing of muscle and motor proteinopathy. The hallmark of CIM is a preferential muscle myosin loss due to increased catabolic and reduced anabolic activity. The ubiquitin proteasome pathway plays an important role, apart from recently identified novel mechanisms affecting non‐lysosomal protein degradation or autophagy. CIM is not reproduced by pure disuse atrophy, denervation atrophy, steroid‐induced atrophy or septic myopathy, although combinations of high‐dose steroids and denervation can mimic CIM. New animal models of critical illness and ICU treatment (i.e. mechanical ventilation and complete immobilization) provide novel insights regarding the time course of protein synthesis and degradation alterations, and the role of protective chaperone activities in the process of myosin loss. Altered mechano‐signalling seems involved in triggering a major part of myosin loss in experimental CIM models, and passive loading of muscle potently ameliorates the CIM phenotype. We provide a systematic overview of similarities and distinct differences in the signalling pathways involved in triggering muscle atrophy in CIM and isolated trigger factors. As preferential myosin loss is mostly determined from biochemistry analyses providing no spatial resolution of myosin loss processes within myofibres, we also provide first results monitoring myosin signal intensities during experimental ICU intervention using multi‐photon Second Harmonic Generation microscopy. Our results confirm that myosin loss is an evenly distributed process within myofibres rather than being confined to hot spots.     

Care of the Patient With a Critical Illness

A method of care applicable to all forms of critical illness is presented. A patient is considered to be critically ill when he is threatened with hypoxia. According to this concept, procedures to understand and solve problems of critical care are coordinated and unified. The relevant physiology and monitoring of the components of the oxygenating system are described. The treatment of patients with impaired function of these components is described.     

cTnI水平与非心源性危重症患者预后的相关性

目的：探讨血清cTnI与非心源性危重症患者病情严重程度和预后的相关性。方法：将66例非心源性危重症患者根据入院后96h内cTnI是否有异常升高,分为高危组和低危组,分析两组患者急性生理和慢性健康状况评分Ⅱ（APACHEⅡ）分值、ICU住院时间、ICU住院费用、机械通气情况、30d病死情况的差异。结果：高危组的APACHEⅡ评分、ICU住院时间、ICU住院费用、机械通气人次、30d内病死人数均高于（多于）低危组（P〈0.05或P〈0.01）。结论：非心源性危重症患者血清cTnI的含量可在相当程度上反映患者病情的严重程度,并对患者的短期病死率预估有一定的帮助;因此cTnI可作为APACHEⅡ评分系统之外评价危重症患者病情与预后的重要指标。     

血液净化疗法在内科危重急症抢救中的作用

目的探讨血液净化技术在内科危重急症抢救中的作用。方法回顾性总结1987年以来我们应用血液净化技术抢救内科危重急症675例患的效果。结果总抢救成功率达89．5％(604／675)。其中急性肾功能衰竭、慢性肾功能衰竭合并严重并发症和其它非。肾性内科危重急症的抢救成功率分别达80．2％(77／96)、92．3％(470／509)、81．4％(57／70)。结论血液净化技术在内科危重急症的抢救中有着十分重要的作用,但其具体实施要因人而异,重视综合治疗。     

广州2例甲型H1N1流感危重症病例临床特点

目的探讨甲型H1N1流感重症病例的临床特征。方法回顾分析2例住院甲型H1N1流感危重症的临床表现、实验室检查结果。结果 2例患者早期均有轻度的流感样症状,发热,咳嗽、咳痰,第3～4天病情加重,气促明显,原有基础疾病症状显著。后期出现多脏器功能不全,以呼吸功能不全出现较早,且严重。实验室检查白细胞计数、中性粒细胞比率增高,淋巴细胞比率减低,肾功能、凝血指标异常。X线胸片两肺均有广泛受累。结论有基础疾病的甲型H1N1流感患者,发病后病情进展较快,易发展为危重症病例,病死率高。对易发展为重症的高危人群,早预防,早识别,早治疗,是降低其死亡率的关键。     

Genetic Susceptibility to Nosocomial Pneumonia,Acute Respiratory Distress Syndrome and Poor Outcome in Patients at Risk of Critical Illness

Genetic susceptibility may partially explain the clinical variability observed during the course of similar infections. To establish the contribution of genetic host factors in the susceptibility to critical illness, we genotyped 750 subjects (419 at high risk of critical illness) for 14 single nucleotide polymorphisms (SNPs) in the xenobiotics detoxification/oxidative stress and vascular homeostasis metabolic pathways. In the group of nosocomial pneumonia (NP; 268 patients) the risk of acute respiratory distress syndrome (ARDS) is significantly higher for the carriers of CYP1A1 rs2606345 T/T genotypes and AhR rs2066853 G/A-A/A genotypes. AGTR1 rs5186 allele C is more common among NP non-survivors. The duration of stay in intensive care units (ICU) is higher for NP patients with ABCB1 rs1045642-T allele. The cumulative effect of the risk alleles in the genes comprising two sets of genes partners (xenobiotics detoxification: CYP1A1, AhR and RAS family: ACE, AGT, AGTR1) is associated with the development of both NP and ARDS.     

Critical Illness in COVID-19: A Sobering Experience for the Intensivist

How to cite this article: Krishna B. Critical Illness in COVID-19: A Sobering Experiencefor the Intensivist. Indian J Crit Care Med 2021;25(9):965–966.

The first coronavirus disease-2019 (COVID-19) case in India was reported on January 30, 2020, from then till date India has reported more than 3,197,000 confirmed cases with 4,28,700 deaths.¹ The severity of COVID-19 infection ranges from mild flu-like symptoms to severe pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure requiring intensive care unit (ICU) admission. The ICU admission rates for patients hospitalized with COVID-19 infection ranged from 6–30%,^2–4 with an average of 21% as reported from a global review.⁵Although COVID-19 is a global pandemic, the burden of the disease has not been uniform throughout the world. Regions that reported rapid community spread led to overburdening of the healthcare systems, with an exponential need for critical care facilities.The COVID-19 infection is caused by a newly discovered coronavirus. Epidemiological data became imperative to bridge knowledge gaps with respect to risk factors, clinical spectrum, morbidity, and mortality of hospitalized COVID-19 patients. Early and transparent data sharing of characteristics and outcomes of critically ill COVID-19 patients would help fellow physicians in other regions to anticipate and plan resources and treatment strategies.Initial epidemiological research publications reported older age, male gender, and hypertension as risk factors for developing severe COVID-19 infection.^2,4,6 The research paper by Pandit et al. reports the experience from a tertiary care hospital in Mumbai, India, in managing critically ill COVID-19 patients.⁷ It is interesting to note that the maximum number of patients admitted to the ICU was in the 40–60 years of age-group (46.8%), and diabetes was reported to be the most common comorbidity followed by hypertension. The ICU mortality was only 10.15% as compared to the results from a recent large meta-analysis that showed an ICU mortality of 40.5%⁸ in these patients. The observed lower mortality could be attributed to the age-group and the low numbers with severe ARDS (13.42%). The authors also discuss important reasons for the observed lower mortality–patients presenting early in the disease to the hospital, strict adherence to infection control, and prudent resource allocation.Existing evidence has shown that severe ARDS of any etiology has a high mortality (46.1%).⁹ A recent large trial from Florida had reported much lower ICU mortality in critically ill COVID-19 patients (19.8%), as compared to other states or the rest of the world.¹⁰ This lower ICU mortality was attributed to several reasons, like younger age, ethnicity, and higher socioeconomic strata of the admitted patients. It was also highlighted in the study that their healthcare systems were never overburdened, and there was sufficient time available to prepare, train manpower, and provide quality care. Strict ARDS ventilation and infection control protocols were also followed.Another recent meta-analysis had reported lower global ICU mortality in COVID-19 patients (28%).¹¹ Then, is the ICU mortality of patients with severe ARDS due to COVID-19 is low, as compared to other causes of ARDS? The heterogeneity in the population, burden of infection, and disparity in availability, accessibility, and provision of care will never give us the true answer.The lessons learned from these studies showing lower ICU mortality are priority in the prevention of rapid spread in the community, so healthcare facilities are not overburdened. This will enable good triaging, early initiation of treatment, and adherence to standard ICU care, simultaneously providing sufficient time and resources, for building surge capacity. These factors could reduce ICU mortality in critically ill COVID-19 patients.     

The Social Negotiation of People's Views on the Causes of Illness

Over the last two decades increasing attention has been given to lay views of health and illness. An important area within this research is the views that different socioeconomic groups hold on the causes of illness. Generally it is concluded that people of lower socioeconomic status are more likely than those of more affluent standing to talk about the causes of illness in lifestyle rather than structural terms that involve overt connections with the material impact of social inequality. We draw on 20 semi-structured interviews with New Zealanders of lower socioeconomic status to explore the ways various causes are assigned to illness. Our participants voice multiple and often contradictory views when assigning cause, and include references to structural issues in addition to lifestyle risk factors and medical ideas about biological functioning and disease. There appears to be a range of sociocultural explanations available for these people to draw on when making sense of illness. We argue that the prevalence of structural explanations may be due, in part, to cultural shifts and increased critical reaction to various social reforms. Our findings support the idea that people's views are socially constructed to account for the complexities of health and illness as part of everyday life.     

测定甲状腺激素在判断重症病例预后中的价值

目的:通过测定重症疾病患者甲状腺激素(TH),判断其在病情严重程度及疾病预后中的价值.方法:把重症疾病分为三组,分别采用放射免疫分析(RIA)测定血清甲状腺激素进行对照,并作统计学处理.结果:与正常人组比较重症疾病组血清T3、FT3显著降低,rT3浓度升高,T4、FT4、TSH无明显变化.结论:非甲状腺疾病重症病例血清T3、rT3、FT3含量变化与疾病严重程度相关,激素含量在治疗中的变化预示疾病转归情况.     

Chronic Critical Illness: Are We Just Adding Years to Life?

How to cite this article: Ramakrishnan N. Chronic Critical Illness: Are We Just Adding Years to Life? Indian J Crit Care Med 2020;25(5):482–483.

Chronic critical illness (CCI) patients require prolonged specialized care for months or years and remain a challenge for intensive care professionals and healthcare.¹ It is common in the elderly although the incidence is noted to decline in the very elderly due to an increase in early mortality in that age-group.² Modern life-sustaining technologies allow us to keep patients alive despite ongoing life-threatening illnesses. However, this comes with a price including cognitive and functional restrictions, the burden of decision-making for caregivers, and the impact on the healthcare system at large.³The Pareto principle, also known as the 80–20 rule is relevant in healthcare in many ways. A rather small number of people (20%) utilize the majority (80%) of health-care consultations and hospital admissions.⁴ The majority (80%) of an individual''s healthcare needs and expenses are in the last 20% of their lives. It is also estimated that 80% of the cost of care is spent in the initial 20% of the hospital stay. However, this may not apply to those with CCI as costs may surge during the hospitalization with clinical changes requiring additional interventions and therapies that may be expensive.Intensive care units (ICUs) are traditionally considered to be expensive,⁵ and every attempt is made to transfer patients out to other areas based on the level of care required. The venue of care of CCI may vary based on the facility and the health-care system. In most countries, step-down units, high dependency units, or transitional care units provide a lower cost option to provide monitored multidisciplinary care. In countries such as the United States, where healthcare is predominantly driven by third-party insurance payers, specialized long-term acute care hospitals and skilled nursing facilities provide an alternative venue of care. However, stringent protocols and guidelines on the level of care that they could provide prompt readmission to hospitals when the patient has any significant changes in clinical status. Patients and families continue to exercise their choice in such payment models despite attempts by the treating team to explain the overall prognosis and quality of life measures. Strategies for effective communication should be implemented for shared decision-making in this scenario.⁶ If survival remains the only goal of therapy, we continue to “cheat” life at any cost.⁷ In predominantly socialized health-care systems such as the National Health Service in the United Kingdom, European countries, Canada, and Australia, the cost of continued care is borne by the government and indirectly by the tax payers. Measures are adopted to provide this long-term care in dedicated wards as ICU beds are limited and in high demand. While efforts are made to cover medically necessary services, some of these countries limit coverage for services such as home health or medications.⁷ In countries such as India, where payment for healthcare is largely “out of pocket,” decisions by the family are not uncommonly driven by the ability to pay for continued care. This is changing over the years with initiatives on healthcare coverage provided by government and private payers but still largely inadequate to cover prolonged illnesses. ICU at home is evolving as a more cost-efficient option in this scenario although adding significant physical, mental, and financial burden to the families. In this study, “talk turkey” about their observations in a retrospective cohort from an academic center, the authors observed that patients with hemodynamic instability requiring vasopressors and those with neurological comorbidities were at greatest risk of CCI. Not surprisingly significant number of patients with CCI were tracheostomized. The cost for a patient with CCI was six-fold while mortality was also significantly higher. The authors do not clearly specify if some of the extended care could have been provided in alternative venues in their facility to reduce the ICU length of stay.CCI leads to sleepless nights for the patient and the family. It is indeed appropriate to apply a concept similar to Spielman''s 3P model of chronic insomnia⁸ while managing patients with CCI by evaluating the following aspects:

• Predisposing factors that include the comorbidities (particularly neurological) that lead to hospitalizations but not necessarily always requiring critical care.
• Precipitating factors such as noncompliance or infections leading to acute on chronic organ failure necessitating organ supports such as ventilation, hemodynamic support, and renal replacement therapy.
• Perpetuating factors including malnutrition, dyselectrolytemia, pressure ulcers, nosocomial infections, iatrogenic issues, and physical aspects such as delayed mobility.

I would like to propose that we evaluate larger cohorts of CCI to develop and validate a scoring system based on the above factors to assist with additional 3Ps in the management which should include the following aspects:

• Prevention—which begins from efficient chronic disease management and also promptly addressing precipitating and perpetuating factors
• Prognostication—to assist the family with patient-centered decision
• Palliation—when appropriate

By utilizing this model, we will be in a position to create value-based programs to provide more appropriate care for those with a chronic critical illness.Mortality has been the most studied outcome in critical illness, and we experience a moment of triumph about increased survival with advances in technologies and therapies. But are we only adding years to life without being considerate of the quality of life added to those years?⁹ Are we saving patients or creating victims?^10,11 Are we communicating efficiently to assist with the decision-making? And most importantly, whose life and money is it anyway? Time to ponder.     

血浆YKL-40浓度对危重症患者并发腹腔间隙综合征的预测作用

目的:揭示危重症患者血浆YKL-40浓度的变化,探讨其对危重症患者并发腹腔间隙综合征的预测价值。方法:收集危重症患者和健康体检人群各98例。健康体检人群静脉血体检时获得,危重症患者静脉血在入院时获得。ELISA检测血浆YKL-40浓度。结果:危重症患者血浆YKL-40浓度(146.8±79.5)ng/ml显著高于健康体检者(39.4±12.5)ng/ml(t=8.749,P<0.01),与APACHEⅡ评分,呈显著正相关性(r=0.591,P<0.01)。28例(28.6%)并发腹腔间隙综合征。多因素分析显示,血浆YKL-40浓度(OR=1.492,95%CI=1.231～2.116,P<0.01)是危重症患者并发腹腔间隙综合征的独立危险因素。ROC曲线分析显示,血浆YKL-40浓度预测危重症患者并发腹腔间隙综合征有显著预测价值(曲线下面积=0.842,95%CI=0.791～0.914,P<0.001),且判定血浆YKL-40浓度>172.4 ng/ml,对预测并发腹腔间隙综合征有82.1%的灵敏度和78.6%的特异度。结论:危重症患者并发腹腔间隙综合征后,血浆YKL-40浓度显著升高,临床检测YKL-40作为有预报价值的标志物,有助于早期判断腹腔间隙综合征的发生。     

Stress,Illness, and Illness Behavior

Abstract

This paper examines adaptation as a trans-active process involving the skills and capacities of individuals and their supporting groups on the one hand, and the types of challenges they face on the other. Many difficulties in understanding stress processes in illness result from the confusion between illness and illness behavior. It is argued that the medical record is as much a history of the individual's behavior and social selection processes as it is a reflection of levels of physical health. Various examples are discussed, illustrating how medical records can be misleading in research examining the relationship between stress and illness, and how influences attributed to stress may be the result of illness behavior. The paper concludes by examining alternative conceptual models for studying the relationships between life challenges, illness behavior and illness.     

Do we have reliable biochemical markers to predict the outcome of critical illness?

Current outcome prediction in critically ill patients relies on the art of clinical judgement and/or the science of prognostication using illness severity scores. The biochemical processes underlying critical illness have increasingly been unravelled. Several biochemical markers reflecting the process of inflammation, immune dysfunction, impaired tissue oxygenation and endocrine alterations have been evaluated for their predictive power in small subpopulations of critically ill patients. However, none of these parameters has been validated in large populations of unselected ICU patients as has been done for the illness severity and organ failure scores. A simple biochemical predictor of ICU mortality will probably remain elusive because the processes underlying critical illness are very complex and heterogeneous. Future prognostic models will need to be far more sophisticated.     

Dysregulation of sodium channel gating in critical illness myopathy

Critical illness myopathy (CIM) is the most common caused of acquired weakness in critically ill patients. While atrophy of muscle fibers causes weakness, the primary cause of acute weakness is loss of muscle excitability. Studies in an animal model of CIM suggest that both depolarization of the resting potential and a hyperpolarized shift in the voltage dependence of sodium channel gating combine to cause inexcitability. In active adult skeletal muscle the only sodium channel isoform expressed is Nav1.4. In the animal model of CIM the Nav1.5 sodium channel isoform is upregulated, but the majority of sodium current is still carried by Nav1.4 sodium channels. Experiments using toxins to selectively bock the Nav1.4 isoform demonstrated that the cause of the hyperpolarized shift in sodium channel inactivation is a hyperpolarized shift in inactivation of the Nav1.4 isoform. These data suggest that CIM represents a new type of ion channel disease in which altered gating of sodium channels is due to improper regulation of the channels rather than mutation of channels or changes in isoform expression. The hypothesis that dysregulation of sodium channel gating underlies inexcitability of skeletal muscle in CIM raises the possibility that there maybe dysregulation of sodium channel gating in other tissues in critically ill patients. We propose that there is a syndrome of reduced electrical excitability in critically ill patients that affects skeletal muscle, peripheral nerve, the heart and central nervous system. This syndrome manifests as CIM, critical illness polyneuropathy, reduced cardiac contractility and septic encephalopathy.     

Chronic intestinal pseudo-obstruction: systematic histopathological approach can clinch vital clues

The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung’s disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.