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Vol. 48. Issue 8.
Pages 445-456 (August 2024)
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Vol. 48. Issue 8.
Pages 445-456 (August 2024)
Original article
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Postintensive care syndrome in patients and family members. Analysis of COVID-19 and non-COVID-19 cohorts, with face-to-face follow-up at three months and one year
Síndrome postcuidados intensivos en pacientes y familiares. Análisis de cohortes COVID-19 y no COVID-19, con seguimiento presencial a los tres meses y al año
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Carola Giménez-Esparza Vicha,b,
Corresponding author
, Beatriz Oliver Hurtadoa,b, Maria Angeles Relucio Martineza,b, Salomé Sanchez Pinoa,b, Cristina Portillo Requenaa,b, José David Simón Simóna,b, Isabel María Pérez Gómeza,b, Fernando Mario Andrade Rodadoa,b, Fadoua Laghzaoui Harboulia,b, Fernando Javier Sotos Solanoa,b, Carlos Augusto Montenegro Mourea,b, Andrés Carrillo Alcaraza,b
a Hospital Vega Baja Orihuela, Alicante, Spain
b Hospital General Universitario Morales Meseguer, Murcia, Spain
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Tables (6)
Table 1. Sociodemographic, clinical, and evolutionary characteristics at the ICU stay.
Table 2. Physical, cognitive, and mental changes at the first post-ICU consultation.
Table 3. Physical and neuropsychological sequelae in second post-ICU consultation.
Table 4. Yearly evolution.
Table 5. Predictive factors of PICS-P.
Table 6. Sociodemographic, clinical, and evolutionary characteristics. Propensity Score Matching Analysis.
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Abstract
Objective

Compare prevalence and profile of post-intensive care patient (P-PICS) and family/caregiver (F-PICS) syndrome in two cohorts (COVID and non-COVID) and analyse risk factors for P-PICS.

Design

Prospective, observational cohort (March 2018–2023), follow-up at three months and one year.

Setting

14-bed polyvalent Intensive Care Unit (ICU), Level II Hospital.

Patients or participants

265 patients and 209 relatives. Inclusion criteria patients: age > 18 years, mechanical ventilation > 48 h, ICU stay > 5 days, delirium, septic shock, acute respiratory distress syndrome, cardiac arrest. Inclusion criteria family: those who attended.

Interventions

Follow-up 3 months and 1 year after hospital discharge.

Main variables of interest

Patients: sociodemographic, clinical, evolutive, physical, psychological and cognitive alterations, dependency degree and quality of life. Main caregivers: mental state and physical overload.

Results

64.9% PICS-P, no differences between groups. COVID patients more physical alterations than non-COVID (P = .028). These more functional deterioration (P = .005), poorer quality of life (P = .003), higher nutritional alterations (P = .004) and cognitive deterioration (P < .001). 19.1% PICS-F, more frequent in relatives of non-COVID patients (17.6% vs. 5.5%; P = .013). Independent predictors of PICS-P: first years of the study (OR: 0.484), higher comorbidity (OR: 1.158), delirium (OR: 2.935), several reasons for being included (OR: 3.171) and midazolam (OR: 4.265).

Conclusions

Prevalence PICS-P and PICS-F between both cohorts was similar. Main factors associated with the development of SPCI-P were: higher comorbidity, delirium, midazolan, inclusion for more than one reason and during the first years.

Keywords:
Post-intensive care syndrome
Patient
Primary caregiver
COVID
Physical sphere
Cognitive sphere
Psychic sphere
Quality of life
Resumen
Objetivo

Comparar prevalencia y características del síndrome post-cuidados intensivos paciente (SPCI-P) y familiar/cuidador (SPCI-F) en dos cohortes (COVID y no COVID) y analizar factores riesgo de SPCI-P.

Diseño

Prospectivo, observacional cohortes (Marzo 2018–2023), seguimiento a tres meses y año.

Ámbito

Unidad de Cuidados Intensivos (UCI) polivalente 14 camas, Hospital Nivel II.

Pacientes o participantes

Pacientes: 265, familiares: 209. Criterios inclusión pacientes: edad > 18 años, ventilación mecánica > 48 horas, estancia UCI > 5 días, delirium, shock séptico, síndrome distrés respiratorio agudo, parada cardiaca. Criterios inclusión familiares: acudir consulta.

Intervenciones

Seguimiento 3 meses y año del alta hospitalaria.

Variables de interés principales

Pacientes: sociodemográficas, clínicas, evolutivas, alteraciones físicas, psíquicas y cognitivas, dependencia y calidad de vida. Familiares: estado mental y sobrecarga física.

Resultados

SPCI-P 64,9%, sin diferencias entre grupos. Pacientes COVID más alteraciones físicas que los no-COVID (P =,028). Estos últimos más deterioro funcional (P =,005), peor calidad de vida (P =,003), más alteraciones nutricionales (P =,004) y deterioro cognitivo (P <,001). 19,1% SPCI-F, más frecuente en familiares de pacientes no COVID (17,6% vs 5,5%; P =,013). Factores predictivos independientes de SPCI-P: primeros años estudio (OR: 0,484), mayor comorbilidad (OR: 1,158), delirium (OR: 2,935), varios motivos de inclusión consulta (OR: 3,171) y midazolan (OR: 4,265).

Conclusiones

Prevalencia de SPCI-P y SPCI-F similar en ambas cohortes. Principales factores asociados a SPCI-P: mayor comorbilidad, delirium, midazolan, haber sido incluido en la consulta por más de un motivo y primeros años del estudio.

Palabras clave:
Síndrome post-cuidados intensivos
Paciente
Cuidador principal
COVID
Esfera física
Esfera cognitiva
Esfera psíquica
Calidad de vida
Full Text
Introduction

Critical illness can alter the life trajectory of patients admitted to the intensive care unit (ICU) and result in a traumatic experience for the family. Therefore, one of the current challenges of intensive care medicine is to promote long-term continuous care beyondthe boundaries of ICU and hospital, through follow-up in post-ICU consultations.1 With adequate prevention, detection, and follow-up, we can minimize the occurrence of symptoms and signs related to the Table 6 (PICS), both in patients (PICS-P) and primary caregivers or family members (PICS-F).2,3

In a systematic review, 60 risk factors were identified for developing PICS-P, approximately half of which were related to the patient and the other half to the ICU.4 Interventions should target modifiable risk factors related to the ICU. The application of the ABCDEF bundle may improve patient-centered care, as well as the experience of patients and their families.5

In COVID-19 patients, multiple risk factors related to PICS6,7 have been identified, in addition to barriers hindering the application of the ABCDEF bundle,8 making this population especially vulnerable to syndrome development. Furthermore, severe acute respiratory illness caused by SARS-CoV-2 infection may cause long-lasting symptoms (“long COVID”), persisting long after hospital discharge and potentially overlapping with PICS, exacerbating its symptoms.9 PICS-F may also have worsened during the pandemic due to distancing from loved ones and difficulties in providing support during bereavement.10 This has led to the recommendation to conduct post-ICU consultations for selected patients, with an initial individualized visit after hospital discharge, to predict, identify, and treat long-term problems related to critical illness.11,12

The main objective of this study is to compare the prevalence and sociodemographic and clinical characteristics of PICS-P and PICS-F in 2 cohorts of patients (COVID vs non-COVID). The secondary objective is to identify risk factors associated with PICS-P.

Patients and methodsStudy design

Prospective, observational study of 2 cohorts of critical patients (COVID-19 and other diagnoses) and their family members. From March 2018 through March 2023, all patients discharged alive from the ICU, aged 18 years or older, who met at least one of the following criteria were included: invasive and non-invasive mechanical ventilation for >48 h, ICU stay > 5 days, delirium, septic shock, ARDS, and cardiac arrest (CA). Also included in the study were all family members or primary caregivers who attended the consultation. Patients with a past medical history of severe psychiatric conditions, severe cognitive deficits, severe functional dependence, and patients transferred to other centers or from geographical areas without the possibility of attending subsequent evaluations were excluded. All patients were informed about the study inclusion and gave their consent. The study was conducted in accordance with the principles set forth in the Declaration of Helsinki13 and was approved by the Hospital Ethics Committee.

Variables

Sociodemographic, clinical, and evolutionary variables related to ICU admission were analyzed. After discharge, variables related to the appearance of physical (musculoskeletal, nutritional, and respiratory), psychological, and cognitive changes, as well as the patient’s degree of dependence and quality of life were evaluated. Variables related to caregiver mental status and physical burden were also analyzed.

Study protocol and follow-up evaluation

An individual face-to-face appointment was scheduled for post-ICU consultation after hospital discharge for patients and primary caregivers, adapted during the pandemic to the epidemiological situation. If the patient had not been discharged during the first appointment, he/she was scheduled for another appointment 1 year after hospital discharge, and depending on the symptoms and test findings, they were referred to other medical specialties. All patients and family members completed a satisfaction survey regarding their ICU stay and the consultation.

All patients underwent medical history taking and a complete physical examination. To assess musculoskeletal changes, muscle strength and atrophy, joint pains and limitations, and paresthesias were evaluated. For respiratory issues, the degree of dyspnea was assessed using the modified Medical Research Council dyspnea scale (mMRC),14 as well as other complications related to orotracheal intubation (granulomas, vocal cord paralysis, etc.). Additionally, patients with dyspnea and/or on mechanical ventilation for >48 h were requested to undergo spirometry. Nutritional status was evaluated using the Malnutrition Universal Screening Tool (MUST).15 Mental status (both of patients and caregivers) was assessed using the Hospital Anxiety and Depression Scale (HADS)16 and the severity scale of post-traumatic stress disorder (PTSD),17 while cognitive function was assessed using the Montreal Cognitive Assessment (MoCA).18 Dependency level was measured using the Barthel Index,19 and quality of life was assessed using the Short Form Health Survey (SF-12) questionnaire.20 Caregiver burden was evaluated using the Zarit Burden Interview21 (Supplementary data. Table S1).

Patients and/or family members met the PICS criteria if they exhibited changes in, at least, 1 of the spheres (physical, psychological, or cognitive).3,12

Statistical analysis

Quantitative variables were expressed as mean ± standard deviation or median (interquartile range), and categorical variables as absolute and relative frequencies. Comparison between categorical variables was performed using Pearson's chi-squared test, the linear trend chi-square test, and Fisher's exact test. Comparison between quantitative variables and a dichotomous categorical variable was conducted using the Student's t-test and the Mann-Whitney U test. Multivariate analysis to analyze independent predictive variables for the development of SPCI was performed using logistic regression, employing the stepwise forward method (PIN < 0.10, POUT < 0.05) to correct for collinearity. The variables introduced in the analysis were clinically relevant, as well as those showing a relationship in the univariate analysis with P values < .20. Propensity score matching analysis was conducted using the nearest-neighbor method without replacement on a 1:1 ratio. Each patient from the COVID group was matched with one from the non-COVID group based on the following variables: age, gender, SAPS III, SOFA at admission, months between discharge and consultation, Charlson Index, ARDS, septic shock, delirium, need for mechanical ventilation (MV)/invasive mechanical ventilation (IMV)/non-invasive mechanical ventilation (NIV) > 48 h, deep sedation, and length of ICU stay (days). The effectiveness of matching was determined by calculating the standardized mean difference, where a value < 10% indicates adequate matching. Comparisons of variables in matched groups were performed using McNemar's test and the Wilcoxon signed-rank test. All comparisons were conducted with 2-tailed tests, and P values ≤ .05 were considered statistically significant. Statistical analyses were performed using IBM SPSS version 27® software (IBM™, Armonk, NY) and R version 3.4.0® software (Copyright 2017 The R Foundation for Statistical Computing Platform™).

Results

A total of 265 patients and 209 family members/caregivers were analyzed. Among them, 104 (39.2%) were admitted for COVID-19 (COVID group) and 161 (60.8%) for other etiologies (non-COVID group).

Sociodemographic, clinical, and evolutionary characteristics during the ICU stay

The main characteristics of the patients from each group are shown in Table 1. Patients from the non-COVID group were older (P < .001), had more comorbidities (P < .001), and higher severity measured by SAPS III (P = .006) and SOFA at admission (P < .001). The length of ICU stay (median, 10 vs 7 days; P < .001) and hospital stay (median, 19 vs 14 days; P < .001) was longer in the COVID group.

Table 1.

Sociodemographic, clinical, and evolutionary characteristics at the ICU stay.

  Total (n = 265)  COVID-19 (n = 104)  Non-COVID-19 (n = 161)  P 
Age  61.7 ± 16.2  56.4 ± 13.1  65.2 ± 17.1  < .001 
Men, n (%)  177 (66.8)  67 (64.4)  110 (68.3)  .510 
Year        < .001 
2018  67 (25.3)  –  67 (41.6)   
2019  41 (15.5)  –  41 (25.5)   
2020  69 (26.0)  54 (51.9)  15 (9.3)   
2021  65 (24.2)  45 (43.3)  19 (11.8)   
2022  24 (9.1)  5 (4.8)  19 (11.8)   
Months elapsed between discharge and consultation  4 (3−6)  4 (3−6)  4 (2−6.5)  .422 
Charlson’s index  2 (1−4)  1 (0−3)  3 (1−5)  < .001 
SAPS III  54.7 ± 11.8  52.4 ± 8.3  56.1 ± 13.5  .006 
SOFA at admission  4.1 ± 2.7  3.2 ± 1.6  4.6 ± 3.0  < .001 
Inclusion criteria, n (%)         
MV > 48 h  151 (57.0)  77 (74.0)  74 (46.0)  < .001 
IMV > 48 h  109 (41.4)  48 (46.2)  61 (37.9)  .182 
Days on IMV  15 (6–25)  14 (6–25)  15 (8–31.5)  .015 
NIV > 48 h  60 (22.6)  41 (39.4)  19 (11.8)  < .001 
Days on NIV  2 (1–4)  2 (1–4)  2 (1–3.5)  .137 
CA  14 (5.3)  2 (1.9)  12 (7.5)  .049 
ARDS  129 (48.7)  102 (98.1)  27 (16.8)  < .001 
Septic shock  109 (41.1)  27 (26.0)  82 (50.9)  < .001 
Delirium  114 (43.0)  34 (32.7)  80 (49.7)  .006 
Various  194 (73.2)  94 (90.4)  100 (62.1)  < .001 
Reason for admission, n (%)        < .001 
Cardiovascular  41 (15.5)  1 (1.0)  40 (24.8)   
Respiratory  133 (50.2)  101 (97.1)  32 (19.9)   
Infectious  40 (15.1)  1 (1.0)  39 (24.2)   
Neurologic  10 (3.8)  –  10 (6.2)   
Postoperative  23 (8.7)  –  23 (14.3)   
Other  18 (6.8)  1 (1.0)  17 (10.6)   
Deep sedation, n (%)  107 (40.4)  46 (44.2)  61 (37.9)  .304 
Days on deep sedation  7 (4.5–11)  6 (3–11)  9 (8–14)  .007 
Dexmedetomidine, n (%)  210 (79.2)  98 (94.2)  112 (69.6)  < .001 
Midazolan, n (%)  49 (18.5)  25 (24.0)  24 (14.9)  .062 
Propofol, n (%)  130 (49.1)  47 (45.2)  83 (51.6)  .312 
Isofluorane, n (%)  19 (7.2)  14 (13.5)  5 (3.1)  .001 
Opioids, n (%)  162 (61.1)  82 (78.8)  80 (49.7)  < .001 
Neuroleptics, n (%)  101 (38.1)  41 (39.4)  60 (37.3)  .724 
Neuromuscular blockers, n (%)  45 (17.0)  36 (34.6)  9 (5.6)  < .001 
Days on neuromuscular blockers  4 (3–7)  5 (3–7)  2 (2–8.5)  .276 
Length of ICU stay, days  8 (5–14)  10 (5–17)  7 (4−11)  < .001 
Length of hospital stay, days  16 (10−27)  19 (13−31.5)  14 (8−25)  < .001 

ARDS, acute respiratory distress syndrome; CA, cardiac arrest; ICU, intensive care unit; IMV, invasive mechanical ventilation; MV, mechanical ventilation; NIV, non-invasive mechanical ventilation; SAPS, Simplified Acute Physiology Score; SOFA, Sequential Organ Failure Assessment.

Drugs associated with analgesia and sedation during the ICU stay

The main drugs used for analgesia and sedation are shown in Table 1. Although there were no differences in the percentage of patients with deep sedation, the duration of deep sedation was longer in the non-COVID group (median of 8 days) bs the COVID (median of 6 days) [P = .007].

Presence of PICS in the first consultation

The relationship between patient groups analyzed, the development of PICS, and the presence of physical, psychological, and cognitive complications at the first consultation are shown in Table 2. A total of 172 (64.9%) patients presented with PICS, with no significant differences between the groups. Patients from the COVID group showed more physical changes vs non-COVID patients (P = .028). Functional physical deterioration (P = .005), poorer quality of life scores (P = .003), nutritional alterations (P = .004), and cognitive impairment (P < .001) were more frequent in the non-COVID group.

Table 2.

Physical, cognitive, and mental changes at the first post-ICU consultation.

  Total patients/families (n = 265/209)  COVID-19 patients/families (n = 104/73)  Non-COVID-19 patients/families (n = 161/136)  P 
PICS- P, n (%)  172 (64.9)  63 (60.6)  109 (67.7)  .235 
Physical changes, n (%)  91 (34.3)  44 (42.3)  47 (29.2)  .028 
Musculoskeletal, n (%)  75 (28.3)  35 (33.7)  40(24.8)  .120 
Nutritional, n (%)  32 (12.1)  5 (4.8)  27(16.8)  .004 
Respiratory, n (%)  60 (22.6)  28 (26.9)  32(19.9)  .181 
MUST, n (%)        .310 
Intermediate risk (1 point)  21 (67.7)  2 (40.0)  19 (70.4)   
High risk (2 or more points)  11 (32.3)  3 (60.0)  8 (29.6)   
Degree of dyspnea, mMRC, n (%)        .037 
215 (81.1)  79 (76.0)  136 (84.5)   
24 (9.1)  9 (8.7)  15 (9.3)   
15 (5.7)  9 (8.7)  6 (3.7)   
6 (2.3)  5 (4.8)  1 (0.6)   
5 (1.9)  2 (1.9)  3 (1.9)   
Other respiratory changes  14 (5.3)  6 (5.8)  8 (5.0)  .776 
Spirometry*, n (%)  77 (47.8)  55 (67.1)  22 (27.8)  < .001 
Spirometric pattern*, n (%)        .440 
Obstructive  2 (2.6)  1 (1.8)  1 (4.5)   
Non-obstructive  50 (64.9)  34 (61.8)  16 (72.7)   
Normal  25 (32.5)  20 (36.4)  5 (22.7)   
Values* (% theoretical value)         
FVC  75 ± 16  79 ± 13  65 ± 13  .002 
FEV1  81 ± 21  87 ± 17  65 ± 22  .005 
Tiffeneau-Pinelloi index  105 ± 14  108 ± 13  99 ± 13  < .001 
Simplified functional impairment, n (%)  72 (27.2)  19 (18.3)  53 (32.9)  .009 
Functional impairment, n (%)        .005 
Independient  193 (72.8)  85 (81.7)  108 (67.1)   
Mild dependence  42 (15.6)  13 (12.5)  29 (18.0)   
Moderat dependence  21 (7.8)  5 (4.8)  16 (9.9)   
Severe dependence  9 (3.3)  1 (1.0)  8 (5.0)   
SF-12 quality of life  48.9 ± 11.8  51.3 ± 9.4  47.2 ± 12.9  .003 
Anxiety, n (%)  59 (22.3)  21 (20.2)  38 (23.6)  .515 
Depression, n (%)  43 (16.2)  18 (17.3)  25 (15.5)  .701 
Patient with PTSD, n (%)  37 (14.0)  15 (14.4)  22 (13.7)  .862 
Simplified cognitive impairment, n (%)  78 (29.4)  16 (15.4)  62 (38.5)  < .001 
Cognitive impairment, n (%)        < .001 
No  187 (70.6)  88 (84.6)  99 (61.5)   
Mild  49 (18.5)  9 (8.7)  40 (24.8)   
Moderate  19 (7.2)  6 (5.8)  13 (8.1)   
Sever  10 (3.8)  1 (1.0)  9 (5.6)   
PICS-F **, n (%)  40 (19.1)  11 (15.1)  29 (21.3)  .273 
Simplified ZARIT familiar burden**, n (%)  28 (13.4)  4 (5.5)  24 (17.6)  .014 
ZARIT familiar burden **, n (%)        .076 
No overload  180 (86.1)  69 (94.5)  111 (81.6)   
Mild  19 (9)  2 (2.7)  17 (12.5)   
Intense  10 (4.8)  2 (2.8)  8 (5.8)   
Familial anxiety**, n (%)  24 (11.5)  9 (12.3)  15 (11.0)  .779 
Familial depression**, n (%)  10 (4.8)  4 (5.4)  6 (4.4)  .747 
Familial PTSD**, n (%)  1 (0.1)  1 (1.4)  –  .349 

FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; mMRC, modified Medical Research Council dyspnea scale; PICS, post-intensive care syndrome; PTSD, post-traumatic stress disorder.

*

In 77 cases where spirometry was performed.

**

In 56 cases could not be determined due to absence of family member.

PICS was present in 40 (19.1%) family members and/or primary caregivers. Only family ZARIT differed between the groups, showing higher burden in non-COVID patient's family members (17.6% vs 5.5% in the COVID group; P = .013).

Referral to different medical specialists (77.4% of the patients) is shown in Supplementary Table S2. Only the referral to Pulmonology was more frequent in the COVID group (20 cases, 19.2%) vs non-COVID-19 group (9 cases, 5.6%) [P < .001].

Evolution at the second consultation

After the first consultation, 184 (69.4%) patients were discharged, and 81 (30.6%) were scheduled for a second consultation (Table 3).

Table 3.

Physical and neuropsychological sequelae in second post-ICU consultation.

  Total (n = 69)  COVID-19 (n = 26)  Non-COVID-19 (n = 43)  P 
PICS-P, n (%)  31 (44,9)  7 (26,9)  24 (55,8)  .019 
Physical sequelae, n (%)        .218 
Yes  17 (24,6)  4 (15,4)  13 (30,2)   
No  24 (34,8)  12 (46,2)  12 (27,9)   
Not applicable  28 (40,6)  10 (38,5)  18 (41,9)   
Functional physical impairment, n (%)        .006 
Yes  12 (17,4)  –  12 (27,9)   
No  24 (34,8)  13 (50,0)  11 (25,6)   
Not applicable  33 (47,8)  13 (50,0)  20 (46,5)   
Anxiety, n (%)        .253 
Yes  11 (15,9)  5 (19,2)  6 (14,0)   
No  28 (40,6)  13 (50,0)  15 (34,9)   
Not applicable  30 (43,5)  8 (30,8)  22 (51,2)   
Depression, n (%)        .280 
Yes  8 (11,6)  4 (15,4)  4 (9,3)   
No  26 (37,7)  12 (46,2)  14 (32,6)   
Not applicable  35 (50,7)  10 (38,5)  25 (58,1)   
PTSD, n (%)        .485 
Yes  8 (11,6)  4 (15,4)  4 (9,3)   
No  23 (33,3)  10 (38,5)  13 (30,2)   
Not applicable  38 (55,1)  11 (46,2)  26 (60,5)   
Cognitive impairment, n (%)        .204 
Yes  9 (13,0)  1 (3,8)  8 (18,6)   
No  30 (43,5)  13 (50,0)  17 (39,5)   
Not applicable  30 (43,5)  12 (46,2)  18 (41,9)   
Consultation discharge after ICU stay, n (%)        .851 
Yes  55 (79,7)  20 (76,9)  35 (81,4)   
No  10 (14,5)  4 (15,4)  6 (14,0)   
Not applicable  4 (5,8)  2 (7,7)  2 (4,7)   

PICS, post-intensive care syndrome; PTSD, post-traumatic stress disorder.

1-year evolution

Mortality could not be determined in 18 of the 265 analyzed patients at 1 year as this time had not yet elapsed since hospital discharge. In the remaining 247 patients, mortality did not differ between the COVID (1 case, 1%) and the non-COVID groups (6 cases, 4.2%) [Table 4]. Both ICU and hospital readmission were more frequent in the non-COVID group (Table 4).

Table 4.

Yearly evolution.

  Total (n = 247)  COVID-19 (n = 104)  Non-COVID-19 (n = 143)  P 
1-year mortality*, n (%)  7 (2.8)  1 (1.0)  6 (4.2)  .244 
ICU readmission at 1 year, n (%)  16 (6.0)  1 (1.0)  15 (9.3)  .005 
Hospital readmission at 1 year, n (%)  61 (23.0)  3 (2.9)  58 (36.0)  < .001 
Time elapsed since discharge until readmission**, n (%)        .518 
<1 month  15 (24.6)  1 (33.3)  14 (24.1)   
1−3 months  18 (29.5)  1 (33.3)  17 (29.3)   
3−6 months  18 (29.5)  1 (33.3)  17 (29.3)   
>6 months  10 (16.4)  –  10 (17.2)   
*

In 18 patients, mortality could not be determined as 1 year had not elapsed since discharge.

**

Out of 61 patients with hospital readmission.

Risk factors for the development of PICS-P

The risk factors for developing PICS in analyzed patients are shown in Table 5. On multivariate analysis, independent predictive factors were identified such as early admission to the study (OR = 0.484; 95%CI, 0.251−0.933), higher Charlson comorbidity index (OR = 1.158; 95%CI, 1.009−1.329), delirium (OR = 2.935; 95%CI, 1.530−5.630), various reasons for inclusion in post-ICU consultation (OR = 3.171; 95%CI, 1.592−6.315), and treatment with midazolam (OR = 4.265; 95%CI, 1.608−11.310).

Table 5.

Predictive factors of PICS-P.

  PICS (n = 172)  Non-PICS (n = 93)  P  Adjusted OR (95%CI) 
Age, years  63.5 ± 16.2  58.5 ± 15.9  .015   
Men, n (%)  113 (65.7)  64 (68.8)  .607   
Years      .071  0.484 (0.251−0.933) 
2018−2019  77 (44.8)  31 (33.3)     
2020−2022  95 (55.2)  62 (66.7)     
COVID-19, n (%)  63 (36.6)  41 (44.1)  .235   
Months between discharge and consultation  4 (3−6)  4 (3−7)  .044   
Charlson’s index  3 (1−5)  1 (0−4)  .005  1.158 (1.009−1.329) 
SAPS III  55.7 ± 11.1  52.8 ± 13.0  .053   
SOFA  4.3 ± 2.6  3.7 ± 2.6  .106   
Inclusion criteria, n (%)         
MV > 48 h  109 (63.4)  42 (45.2)  .004   
IMV > 48 h  85 (49.4)  24 (25.8)  < .001   
Days on IMV  15 (6−25)  13 (8−30)  .020   
NIV > 48 h  39 (22.7)  21 (22.6)  .986   
Days on NIV  2 (1−4)  2 (1−4.5)  .201   
CA  10 (5.8)  4 (4.3)  .599   
ARDS  82 (47.7)  47 (50.5)  .656   
Septic shock  80 (46.5)  29 (31.2)  .016   
Delirium  94 (54.7)  20 (21.5)  < .001  2.935 (1.530−5.630) 
Various  136 (79.1)  58 (62.4)  .003  3.171 (1.592−6.315) 
Reason for admission, n (%)      .843   
Cardiovascular  25 (14.5)  16 (17.2)     
Respiratory  85 (49.4)  48 (51.6)     
Infectious  29 (16.9)  11 (11.8)     
Neurologic  6 (3.5)  4 (4.3)     
Postoperative  14 (8.1)  9 (9.7)     
Other  13 (7.6)  5 (5.4)     
Deep sedation, n (%)  84 (48.8)  23 (24.7)  < .001   
Days on deep sedation  5 (3−9)  3 (2−6)  < .071   
Dexmedetomidine, n (%)  145 (84.3)  65 (69.9)  .005   
Midazolan, n (%)  43 (25.0)  6 (6.5)  < .001  4.265 (1.608−11.310) 
Propofol, n (%)  99 (57.6)  31 (33.3)  < .001   
Isofluorane, n (%)  15 (8.7)  4 (4.3)  .183   
Opioids, n (%)  107 (62.2)  55 (59.1)  .625   
Neuroleptics, n (%)  85 (49.4)  16 (17.2)  < .001   
Neuromuscular blockers, n (%)  37 (21.5)  8 (8.6)  .008   
Length of ICU stay, days  8 (5−18)  7 (4−10)  < .001   
Length of hospital stay, days  18 (10−35)  13 (9−21)  .001   
Patient evolution through matched propensity score analysis

After adjusting for multiple confounding variables through matched propensity score analysis, the development of PICS did not differ between the COVID and non-COVID groups (Table 6). Only nutritional changes (P = .021), hospital readmission (P < .001), and worse quality of life at the follow-up (SF-12 46.3 ± 12.5 vs 50.3 ± 10.4; P = .037) were more frequent in the non-COVID group.

Table 6.

Sociodemographic, clinical, and evolutionary characteristics. Propensity Score Matching Analysis.

  COVID-19 (n = 70)  Non-COVID-19 (n = 70)  P  SMD (%) 
Age  59.2 ± 16.7  59.5 ± 13.8  .868 
Men, n (%)  42 (60)  40 (60)  > .999  – 
Months between discharge and consultation  4 (3−5.2)  4 (3.6)  .737  5.8 
Charlson’s index  1 (1−3)  1 (1−2.5)  .682  3.2 
SAPS III  54.7 ± 9.9  54.2 ± 9.4  .708  4.5 
SOFA at admission  3.4 ± 1.8  3.5 ± 2.0  .889  1.7 
Inclusion criteria, n (%)         
MV > 48 h  44 (62.9)  42 (60.0)  .860  4.2 
IMV > 48 h  32 (45.7)  34 (48.6)  .774  3.8 
NIV > 48 h  22 (31.4)  18 (25.7)  .875  6.9 
Deep sedation, n (%)  31 (44.3)  29 (41.4)  .871  3.9 
Dexmedetomidine, n (%)  66 (94.3)  64 (91.4)  .687  9.7 
Midazolan, n (%)  16 (22.9)  13 (18.6)  .664  7.8 
Propofol, n (%)  42 (60.0)  40 (60.0)  > .999  – 
Isofluorane, n (%)  6 (8.6)  5 (7.1)  > .999  5.3 
Opioids, n (%)  54 (77.1)  52 (74.3)  .839  4.9 
Neuroleptics, n (%)  31 (44.3)  28 (40.0)  .664  7.8 
Neuromuscular blockers, n (%)  21 (30.0)  23 (32.9)  .687  9.7 
Length of ICU stay. days  9 (5–19)  8 (5–15)  .220  3.1 
Length of hospital stay. days  20 (15–35)  16 (9−34)  .212  0.6 
PICS, n (%)  42 (60.0)  43 (61.4)  > .999   
Physical changes, n (%)  32 (45.7)  20 (28.6)  .081   
Musculoskeletal, n (%)  21 (30.0)  22 (31.4)  > .999   
Nutritional, n (%)  5 (7.1)  13 (18.6)  .021   
Respiratory, n (%)  20 (28.6)  13 (18.6)  .189   
Simplified functional impairment, n (%)  13 (18.6)  18 (25.7)  .359   
Anxiety, n (%)  16 (22.9)  19 (27.1)  .629   
Depression, n (%)  14 (20.0)  13 (18.6)  > .999   
PTSD, n (%)  9 (17.1)  9 (12.9)  .648   
SF-12 quality of life  50.3 ± 10.4  46.3 ± 12.5  .037   
Simplified cognitive impairment, n (%)  9 (12.9)  17 (24.3)  .115   
PICS-F *, n (%)  5 (11.6)  8 (12.5)  > .999   
Simplified ZARIT familiar burden**, n (%)  2 (4.7)  6 (9.4)  .500   
Familiar anxiety*, n (%)  5 (11.6)  7 (10.9)  > .999   
Familiar depression*, n (%)  1 (1.4)  2 (2.9)  > .999   
1-year mortality rate**, n (%)  2 (2.9)  2 (3.1)  > .999   
ICU readmission at 1 year, n (%)  1 (1.4)  7 (10.0)  .070   
Hospital readmission at 1 year, n (%)  1 (1.4)  23 (32.9)  < .001   

PICS, post-ICU syndrome; PTSD, post-traumatic stress disorder; SMD, standardized mean difference; ICU, intensive care unit.

*

In 33 cases, determination was not possible due to absence of family member.

**

In 5 cases, determination of 1-year survival was not possible.

Discussion

The most important finding of this study is that the prevalence of PICS-P and PICS-F was similar in both cohorts (COVID and non-COVID) at the first follow-up consultation, with rates of 65.2% and 19.1% in both patients and family members, respectively. However, at the 1-year follow-up, a higher percentage of non-COVID patients still exhibited signs or symptoms of PICS-P. Additionally, there were differences in the type of changes exhibited by both cohorts of patients and family members. In patients, the most frequent were physical, especially in the COVID group (42.3% vs 29.2%, P = .028), at the expense of a higher, albeit not significant, number of musculoskeletal and respiratory changes, which, however, were more frequent in non-COVID patients at the 1-year follow-up. Regarding the degree of functional dependence and quality of life, these were worse in the non-COVID patient group.

There is significant variability in the prevalence of PICS-P and PICS-F2 across different studies, and the most common changes depend on the characteristics of the patienets and the evaluation methods used. In COVID-19 patients, this variability is equal to or even greater. Various studies conducted in France,22 the United States,6 and the Netherlands,23 involving COVID-19 patients on mechanical ventilation, have shown very significantly different results. In Spain, a study conducted on ventilated COVID-19 patients found that approximately 3 out of every 4 patients met PICS criteria at the 3-months follow-up.24 One of the main limitations of these studies is the lack of comparison with a non-COVID-19 patient cohort, and the fact that most follow-ups (except the Spanish study) were not conducted in person.

Several authors have reported that the physical, psychological, and cognitive deficits observed in ICU survivors after COVID-19 are comparable to those observed in patients with other diseases.25,26 Additionally, it has been demonstrated that ARDS survivors have persistent functional limitations 1 year after ICU discharge due to muscle atrophy and weakness,27 and that the inability to exercise even at the 5-year follow-up is mainly due to extrapulmonary causes.28–30 Similarly, prolonged mechanical ventilation (MV) is a risk factor for long-term physical changes.24 This would explain the higher percentage of functional changes reported in COVID patients who were primarily included due to MV > 48 h and ARDS.

However, age,31 pre-existing comorbidities,1 nutritional changes, and disease severity4 have been identified as determinants of poor prognosis related to increased functional dependency and worse long-term quality of life, all of which are present in our non-COVID patients. Furthermore, the severity of illness upon ICU admission has also been associated with a higher rate of ICU and hospital readmission, both significantly higher in our non-COVID patient group.

Cognitive impairment was also more common in non-COVID patients, due to the older age of these patients, but also to the longer duration of deep sedation and higher incidence of delirium, both factors clearly associated with long-term cognitive impairments.32,33 Deep sedation contributes to increased mortality and worsens clinical outcomes, both in the short- and long-term (delirium and cognitive impairment).34,35

Therefore, although physical changes (primarily musculoskeletal and respiratory) were more frequent in the COVID group, as a consequence of their respiratory disease (more patients with ARDS and mechanical ventilation > 48 h), the greater presence of other predictive factors of poor prognosis in the non-COVID patient group, such as older age, comorbidities, worse nutritional status, and disease severity, influenced and significantly impacted the quality of life and degree of dependency within the first few months of follow-up, as well as the persistence of PICS-P 1 year after hospital discharge. These factors also had an impact on the hospital and ICU readmission rates at 1 year.1 In addition to these non-modifiable factors, other factors external to the patient and preventable in the ICU, such as deep sedation and delirium, contributed to a greater long-term cognitive decline in COVID patients.

PICS-F was present in 19.1% of family members and/or caregivers. The most frequent change was family burden (P = .014), which was significantly higher in non-COVID patients' families (17.6% vs 5.5%; P = .013), followed by anxiety. There is great variability in the prevalence of PICS-F in different studies,36,37 with mental and physical changes being described in up to 60% and 40%, respectively, depending on the variables analyzed and methods used. Similarly, multiple risk factors for PICS-F38 have been identified such as disease severity, communication, female sex, etc. In our series, the incidence was lower, and caregivers who experienced greater burden were those of patients with more dependency and worse quality of life.

The risk factors identified in our patients for developing PICS-P were greater comorbidity, delirium, several reasons for post-ICU follow-up consultation, treatment with midazolam, and being admitted within the early years of the study. The association of pre-existing comorbidity, delirium, and other factors such as age with PICS has been previously discussed. Additionally, the use of midazolam has also been identified as an important factor associated with this syndrome.39 Regarding being admitted in the early years of the study, this relationship could be due to the greater implementation of the ABCDEF bundle throughout the study period, which has been shown to improve the patients' long-term prognosis.1,40 In our ICU, we gradually implemented a program to prevent PICS (optimization and monitoring of analgosedation and delirium, flexible visiting hours, improvement of communication and entertainment through clocks, TVs, augmentative communicators, etc.), culminating in 2020 (during the pandemic) with the addition of a physical therapist and a psychologist into our unit. This may have influenced the admission in the early years of the study as a risk factor for developing PICS and COVID patients presenting with less physical, functional, and cognitive deterioration than non-COVID patients (most of whom were admitted before the pandemic).

This work has strengths and weaknesses. It is a study with face-to-face follow-up, including a relevant number of patients and family members, and compares 2 different cohorts: COVID and non-COVID, which is a strength of the study. Regarding weaknesses, firstly, due to its single-center design, the generalization of results may be compromised to some extent. Secondly, due to follow-up, some of the evolving variables have not yet been measured at the time of this work. Finally, although the inclusion of analyzed variables was certainly comprehensive, we may have overlooked some important variables. Nevertheless, we believe that the study's conclusions remain valid. We propose future research based on a national registry of PICS.

Conclusions

There were no differences in the incidence of PICS in patients and family members of both cohorts (COVID vs non-COVID) at the first follow-up consultation, although it was more frequent in non-COVID patients at 1 year. The main factors associated with developing PICS-P were greater comorbidity, presence of delirium, sedation with midazolam at the ICU stay, as well as being included in the consultation for more than 1 reason and during the early years of the study, when the implementation of the ABCDEF bundle was lower.

Funding

No total or partial funding was received to conduct study, nor any type of grant or financial support.

Conflicts of interest

None declared.

Authors’ contributions

Carola Giménez-Esparza Vich: Data mining. Elaboration and drafting of the article.

Beatriz Hurtado Oliver: Data mining. Drafting.

Maria Angeles Relucio Martinez: Data mining. Drafting.

Salomé Sanchez Pino: Data mining.

Cristina Portillo Requena: Data mining.

José David Simón Simón: Data mining.

Isabel María Pérez Gómez: Data mining.

Fernando Mario Andrade Rodado: Data mining.

Fadoua Laghzaoui Harbouli: Data mining.

Fernando Javier Sotos Solano: Data mining.

Carlos Augusto Montenegro Moure: Data mining.

Andrés Carrillo Alcaraz: Statistical analysis and Drafting.

Acknowledgments

We wish to thank Dr. José Manuel Añón Elizalde and Dr. José Abelardo García de Lorenzo for providing us with all the necessary assistance and documentation to initiate post-ICU consultations.

Appendix A
Supplementary data

The following is Supplementary data to this article:

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