Epidemiology and Costs of Postsepsis Morbidity, Nursing Care Dependency, and Mortality in Germany, 2013 to 2017

Key Points Question How common are new and co-occurring medical, cognitive, or psychological diagnoses, new nursing care dependency, and postacute mortality among individuals who survive sepsis? Findings In this cohort study of 116 507 survivors of hospital-treated sepsis in Germany, nearly three-quarters had new medical, cognitive, or psychological diagnoses; nearly one-third were newly dependent on nursing care; and more than of 3 in 10 died in first year post sepsis. New diagnoses co-occurred in one-quarter of participants and affected sepsis survivors irrespective of preexisting diagnoses, sepsis severity, and intensive care unit treatment. Meaning These findings suggest that postsepsis morbidity may be more common and severe than previously believed, calling for increased efforts to prevent and treat the sequelae of severe infections.


Postsepsis morbidity concept and operationalization
To identify diagnoses associated with postsepsis morbidity, we conducted a comprehensive literature review on reviews, round table/position papers, and large cohort studies investigating impairments following acute care treatment with sepsis or intensive care treatment. 1,9,11,36,[39][40][41] We classified diagnoses as medical, psychological, or cognitive (Table   S1). For the identification of each diagnosis in hospital discharge and outpatient data, relevant ICD-10 codes or procedural codes were identified (i) from prior literature, 42-45 or (ii) in the ICD-10-GM and list of procedural codes, to ensure completeness of definitions. The classification and ICD-10-GM definitions were reviewed in an iterative process by experts from the following fields: • for sepsis rehabilitation Klinik Bavaria, Kreischa (Prof. Oehmichen, Dr. Sauter) • from the SMOOTH 46 study group (Dr. Konrad Schmidt, A. Freytag) • from the REPAIR 47 study group (PD Dr. Rosendahl, Dr. Gawlytta) • for sepsis-related pain (Prof. Meißner) and neurology/geriatrics (PD Preul) • from the SEPFROK expert panel (Prof. Vollmar (general medicine), Prof. Janssens (intensive care), Dr. Hecker (patient safety), A. Trumann (sepsis survivor), Dr.

Case identification: Definitions and Codes
The identification of sepsis patients in our study was based on the following ICD-10-GM codes in health claims data. At least one of the codes had to be coded as primary and secondary discharge diagnosis. During the complete observation period, sepsis coding was based on the sepsis-1/2 criteria in Germany. Therefore, severity was classified as: sepsis -all forms; severe sepsis (including septic shock); septic shock; and non-severe sepsis.
Sepsis ICD-10-GM Codes: A02.1 Salmonella sepsis A20.0 Bubonic plague A20.7 Septicaemic plague A21.7 Generalized tularaemia A22.7 Anthrax sepsis A24.  (1) first sentence of the Hospital Funding Act; Internal transfer with a change between the DRG fee ranges according to section 17b (1)first sentence of the Hospital Funding Act; Relocation; Discharge before resumption with reclassification; Discharge before resumption with reclassification due to complication; Discharge or transfer with subsequent readmission; Case closure (internal transfer) when changing between full, day-care and ward-equivalent treatment; Start of an outside stay with an absence past midnight (BPflV area -for the specialist department for laying); Ending an outside stay with an absence past midnight (BPflV area -for pseudo specialist department 0003); Discharge at the end of the year if accepted in the previous year (for the purposes of Billing - § 4 PEPPV); Beginning of a period without direct patient contact (station equivalent treatment); Termination of a period without direct patient contact (ward equivalent treatment -for pseudo-specialist department 0004); As data on outpatient diagnoses, cases, case-related therapies and corresponding costs in Germany are available on only a quarterly basis, data from quarters 1-4 prior to hospital admission were included in the 12 months look-back, respectively.
Both primary and secondary hospital discharge diagnoses as well as outpatient diagnoses labeled as confirmed diagnoses by the treating physicians 23 were included in the definition of pre-sepsis health impairments.

Employment Status Definition
Employed Mechanical ventilation and respiratory support in adults 8-712 Mechanical ventilation and respiratory support in children and adolescents

8-714
Special procedure for mechanical ventilation in the case of severe respiratory failure 8-70 Access for mechanical ventilation and measures to maintain the airway

8-71
Mechanical ventilation and respiratory support via a mask or tube and ventilation weaning Heart and heart-lung transplantation 5-555 Kidney transplantation 5-335 Lung transplantation 5-5281 Transplantation of a pancreas segment 5-5282 Transplantation of the pancreas (whole organ) 5-4676 Small intestine transplantation Prior major surgery OPS Codes: 5-32 Excision and resection of lung and bronchus 5-33 Other operations on lung and bronchus 5-34 Operations on the chest wall, pleura, mediastinum and diaphragm 5-35 Operations on the valves and septa of the heart and pericardial vessels 5-36 Operations on the coronary vessels

5-37
Surgical treatment of arrhythmias and other operations on the heart and pericardium 8-851 Bypass surgery (using the heart-lung machine) 5-38 Incision excision and occlusion of blood vessels.

5-39
Other operations on blood vessels 5-42 Surgery on the oesophagus 5-43 Incision, excision and resection of the stomach 5-44 Extended stomach resection and other operations on the stomach 5-45 Incision, excision, resection and anastomosis of the small and large intestine 5-46 Other operations on the small and large intestine 5-47 Operations on the appendix 5-48 Operations on the rectum 5-49 Operations on the anus 5-50 Operations on the liver 5-51 Operations on the gallbladder and bile ducts 5-52 Operations on the pancreas 5-53 Abdominal hernia repair 5-54 Other operations in the abdominal region 5-78 Operations on other bones 5-79 Reduction of fractures and dislocations 5-80 Open joint surgery 5-81 Arthroscopic joint surgery 5-82 Prosthetic joint and bone replacement 5-83 Operations on the spine 5-84 Operations on the hand 5-85 Operations on muscles, tendons, fasciae and bursae

5-86
Replantation, exarticulation and amputation of extremities and other operations on the organs of locomotion 5-01 Incision (trepanation) and excision of the skull, brain and meninges 5-02 Other operations on the skull, brain and meninges 5-03 Operations on the spinal cord, spinal meninges and spinal canal 5-04 Operations on the nerves and nerve ganglia 5-05 Other operations on the nerves and nerve ganglia 5-55 Operations on the kidneys 5-56 Operations on the ureters 5-57 Operations on the bladder 5-58 Operations on the urethra 5-59 Other operations on the urinary organs 5-60 Operations on the prostate and seminal vesicles 5-61 Operations on the scrotum and tunica vaginalis testis 5-62 Operations on the testicles 5-63 Operations on the spermatic cord, epididymis and vas deferens 5-64 Operations on the penis 5-65 Operations on the ovary 5-66 Operations on the fallopian tubes 5-67 Operations for facial bone fractures 5-68 Incision, excision and removal of the uterus 5-69 Other operations on the uterus and operations on the parametria 5-70 Operations on the vagina and recto-uterine pouch 5-71 Operations on the vulva 5-72 Childbirth with breech presentation and instrumental delivery 5-73 Other operations to induce labour and during the birth 5-74 Caesarean section and child development 5-75 Other obstetric operations 5-87 Excision and resection of the breast 5-88 Other operations on the breast 8-989 Surgical complex treatment in cases of severe infection

Postsepsis morbidity
As data on outpatient diagnoses, cases, case-related therapies and corresponding costs in Germany are available on only a quarterly basis, data from quarters 1-4, 5-8 and 9-12 following the quarter of the index hospitalization discharge date were included in the 12, 24 and 36 month follow-up, respectively.
Both primary and secondary hospital discharge diagnoses as well as outpatient diagnoses labeled as confirmed diagnoses by the treating physicians 23 were included in the definition of post-sepsis diagnoses. Unspecified organic mental disorder due to brain damage and dysfunction and to physical disease F07.8 Other organic personality and behavioural disorders due to brain disease, damage and dysfunction F07.9 Unspecified organic personality and behavioural disorder due to brain disease, damage and dysfunction G30 Alzheimer disease G31.0 Circumscribed brain atrophy G31.1 Senile degeneration of brain, not elsewhere classified G31.9 Degenerative disease of nervous system, unspecified G32* Other degenerative disorders of nervous system in diseases classified elsewhere All ICD-based definition for the baseline and index hospitalization characteristics can be found in Supplement 1. Abbreviations: CCI = Charlson Comorbidity Index, unweighted; IQR = Interquartile range; SD = Standard deviation * eligibility for long-term care benefits in line with the German Social Code, ranging from Grade 1: "Little impairment of independence" up to Grade 5: "Hardship cases" ** Total health care costs include cost for hospitalizations, outpatient consultations, medication, treatments (e.g. physical or occupational therapy) and rehabilitation. ***Defined by ICD code indicating an infectious source, as indicated in methods supplement. Note that multiple sites of infection were possible.  12,982 (19,255); 6,194 (2,066, 15,891) 13,192 (20,233); 6,495 (2,203, 16,114) 13,344 (21,175); 6,141 (1,992, 15,995) 12,935 (18,877); 6,423 (2,194, 15,985) 3,089 (9,001); 443 (70, 1,869) IQR = Interquartile range; SD = Standard deviation * any ICD-10 code for organ dysfunction, not necessarily linked to infection/sepsis, as the coding of organ dysfunction in sepsis patients is not mandatory in Germany ** eligibility for long-term care benefits in line with the German Social Code *** Total health care costs include cost for hospitalizations, outpatient consultations, medication and treatments (e.g. physical or occupational therapy) and rehabilitation.