‘VIA MEDICA CASE REPORTS sealed Advanced therapeutic methods for the treatment of meningococcal septic shock — case report Wiestawa Duszyriska, Jakub Smiechowicz, Barbara Adamik, Stanislaw Zielifiski, Andrzej Kubler Chair and Department of Anaesthesiology and intensive Therapy, Wroclaw Medical University, Poland Abstract Background, Meningitis caused by Neisseria meningitidisis primarily a disease of children and young adult. septic shock complicates the course of meningitis it must be treated in the intensive care unit. Case report. A 18.years old man with symptoms of meningococcal meningitis and clinical features of septic shock. was admitted to the ICU. patient with tachycardia (heart rate 140 min) required vasopressor to maintain blood pressure (noradrenalin 1 yg kg" min) on admission. Respiratory failure developed (respiratory rate of 40 min’ a0, 79%, PaO, /O, ratio =55) and mechanical ventilatory support was used. The presence of Neisseria meningitidis was confirmed withthe rapid latex agglutination test Cefotaxime with vancomycin wasadministeredon day one and vancomycin was replaced with meropenem on day two. Aditionallyto the standard treatment of septic shock and ‘multiorgan failure, hemoperfusion with LPS adsorber was performed to eliminate endotoxins from the bloodstream, and drotrecogine alfa wasadministered, Hemoperfusion was performed twice for2 hours session and blood endotoxin activity decreased from 0.75 EAU do 0.4 EAU after 48 hours. Patient was admitted with signs of acute kidney injury and required continuous renal replacement therapy (Ca-Ca CVWHD, CWVHDP. Conclusions. Rapid pathogen identification, adequate antimicrobial therapy and endotoxin elimination from the. bloodstream improved hemodynamic and respiratory parameters ofthe patient. Application of routine plus non- -standard methods of treatment of septic shock prevented the progression of the biological cascade in sepsis and improved patient’ clinical condition Key words: septic shock, meningococcal meningitis, endotoxin elimination, LPS Adsorber Anaesthesiology Intensive Therapy 2072, vol 44, no4, 212-216 Cerebrospinal meningitis (CSM) caused by Neisseria meningitidis affects mainly children and young people. Its estimated annual incidence in Europe is 0.5/100000 Viduals. The lowest incidence rates are reported in Poland, Hungary and italy, while the highest ones in eland, Iceland and Malta [1, 2,31. Group B Neisseria meningitidis accounts for 40-95% of CSM cases whereas group C meningacocci cause 3-55% ofinfections, however their course is generally ‘more severe [3] The mortality in these infections increases with age; this increasing tendency is visible since the age f 20 reaching the highest mortality (20%) in patients over 65 years of age [1]. Patients with cerebrospinal meningitis accompanied by septic shock have to be promptly admit: ted to the ICU and the guidelines of the Surviving Sepsis Campaign should be considered [4]. Such aform of disease 212 is characterized by rapid clinical course and high mortality (> 50%). Half of deaths occur within the first 12 hours after admission to hospital 5) ‘The prosent report i the fst Polish description of the ‘treatment of septic shock in the course of Neisseria menin- gitds-induced meningitis using the Alteco LPS Adsorbe, ‘continuous citrate haemodialysis and infusion of recombi: nant activated protein C(rAPC). CASE REPORT ‘An 18year-old male patient without medical history was admitted tothe ICU from the department of infactious diseases due to septic shockin the course of meningococcal ‘meningitis. The acute physiology and chronic health eval ationl APACHE I) score was29and sequential organ failureWiestowe Duseysa etal Treatment of meningococcal septic shock assessment (SOFA) score 15. The disease started on thesame day and manifested with headache, fever to 40°C, vomiting and rapidly increasing haemorrhagic skin lesions over the entire body. During the several-hour stay inthe department of infectious diseases (11.40 pm-2.00 am), the patient was conscious; massive haemorrhagic lesions on the skin and oral mucosa and meningeal symptoms were observed. The laboratory abnormalities are presentedin Table 1.Thehead CT scan did not reveal any pathologic changes. The blood was sampled for microbiological testing (at minute 40 after hospital admission) and the patient received cefotaxime (20 9), crystalline penicilin (6 min units), amikacin (1.0 g), and dexamethasone (8 mg)-The lumbar puncture and CSF collection for the diagnosis ofcerebrospinal meningitis were abandoned due to clotting disorders. Arterial pressure was found to be decreasing; therefore the central vein catheter was placed, the noradrenaline infusion initiated and the patient was transferred to ICU for further treatment. On admission to ICU, the patient presented the fea- tures of shock; circulation was unstable. Tachycardia was observed — 140 min arterial pressure was 140/80 mm Hag at the continuous infusion of noradrenaline in a dose of 1 ug kg" min’, Due to respiratory failure (number of respirations 40 min’ $20, 79%, PaO,/FiO, 58), the pationt was intubated immediately after admissionand mechanical Ventilation wasstarted Before intubation, the patient wasin verbal contact albeit confused. The skin ofthe entire body, particularly of limbs, was covered with merged haemor- ‘hagiclesions Numerous bilateral ales were heard over the entire lung fields. The chest X-ray showed massive, patchy and infiltrative changes as well as blurring of both lung fields characteristic of acute respiratory distress syndrome Table 1 Assesment of patients clinical status on CU adision and schage meter 1eUadmision _1CU discharge Body temparature ea 3B Wace) zeal 1505 ce img) ma sas Procakitonin tng"! >2000 196 Poteet (GL") 350 1480 ast) an 5 Are 1616 » Serum creatinine ng a) aa ant Tota irbin (mg dt) 26 05 Prothrombin tio) 4 02 aeTT 660) 169 aan Demers mt") ma 168 Lctates mal) 758 07 “aca cotnuus ea eplacement theca olguia dss thapy Within an hour after ICU admission, blood was re-sam- pled for microbiological testing (pharyngeal swab and bronchial tree secretion were aso collected); the patient received vancomycin 1.0 g and amikacin was discontin ued. Cefotaxime in a dose of 2 mg every 12 h (tailored for continuous renal replacement therapy) was continued, Eighthours ater admission the presence oftypeC Neisseria _meningitdis antigen was confirmed using the Wellcogen Bacterial Antigen Kit Rapid latex agglutination test. The testis designed for identification of antigens of group B “Streptococcus, type BH. inuenzae S, pneumoniae: group A, C.¥,W135.N. meningitdes, group 8 N. meningitidis in body fluids. Since the latex test results excluded preumococcal Infection, vancomycin was withdrawn. ‘On treatment day 1, the patient's circulation was un- stable and he required noradrenaline in the incremental doses £01.09 kg" min (5 mg h!) and adrenaline in in- travenousinfusion in a dose of 083 yg kg" min" (4mg"") (On the following day, the infusion of adrenalin was dis continued and the dose of noradrenaline increased to 24g kg min" (10 mg fr. During treatment day 1, extracorporeal endotoxin elimi nation with Alteco LPS adsorber column (Rlteco Medical AB, Lund, Sweden) was used. Adsorber consisted of polyethyl ene discs coated with the antibody specifically binding en- dotoxins. The blood flow through the adsorber was 150 mL rmin-!and was maintained using the renal replacement ther apy machine (Fresenius Medical Care, Hamburg, Germany). The efficacy of therapy was monitored by measurements of ‘endotoxinactivityin blood. The hemiluminescence method (Endotoxin Activity Assay — EAA, SPECTRAL Diagnostics, Canada) was employed, in which the value < 0.4 EAU (en dotoxin activity units considered low, 04-0 59 EAU ind ‘atesendotoxaemia whereas 06 confirms endotoxaemia and septic shock. The baseline activity of endotoxinsin our patient was 0.75 EAU: 24h after the fist haemoperfusion procedure, the activity decreased to 0.68 EAU, and 24h after the second procedure to 0.4 EAU. Te circulatory ef ficiency significantly improved afte the second procedure ‘of haemopertfusion Table 2). ‘The patientlungs were mechanically ventated inital Iyusing the PCV mode with FiO, 1.0, reaching PaO, =87 mm Hg. Short-term, several-minute high-frequency oscilatory ventilation (HFOV) with FiO, 1.0 did not improve arterial blood oxygenation (Pa0,/FiO, = 66), and during the pro- ‘cedure abundant amounts of feamy-bloody secretions flown out ofthe endotracheal tube. The retum to pressure controlled ventilation enabled to obtain satisfactory a0, values on day 1. ‘Athour3 after ICU admission, the intravenous infu of drotiecogin-a wasstartediina dose of 24yg ka" day "and continued for 96h. 213Anaesthesiol Intensive Ther 2012 sue 44,04 212-216 ‘Table Changes in LPS concentatons and haemodynamic parametesafter LPS elimination procedures using the Alteco LPS adsorber Parameter Beforethefistendotoxinlimination __24hafterthefistprocedure __24haferthe second procedure Les(eau) 076 088 ou AP rm Ha) @ % 100 Pa0,/F0, o 166 a Noradrerlin ogg" mi 08 hg mi 025 9 hg! min! AU —endtonactity nits MAP — mean ae pres ‘At hour 4 after ICU admission, continuous veno-venous haemodialysis was initiated with regional anticoagulation us- ingeitrates —C.CaCWWHD (multiFitrate KIT C-CA, Fresenius Medical Care, Hamburg Germany) continued for3 days. Since septic shock persisted and features of multiple organ failure increased, on day 2, meropenem was additionally included into empiric treatment, 2 mg every 8 h. The microbiological results of blood collected on admission to the department of infectious diseases received on ICU treatment day 3 con- firmed the presence of N. meningitis. MIC for peniciins was 0.25 jig mL, which, according to the EUCAST recom= ‘mendations, did not allow de-escalation. However, within the range of MIC values, the strain showed suscepti cefotaxime and meropenem, which were used in combined ‘therapy since the clinical responce tomonotherapy was poor. Cefotaxime wasadministeredfor20 successive days whereas meropenem for 13 days. ‘The features of acute renal injury persisted: therefore, jonce C-CA CVVHD was completed, continuous veno-venious haemodiafitration (CWWHDF) was initiated with systemic an ‘coagulation with heparin The therapy was continued until day9;between day 10nd 25, haemodialysis procedures were performedona daily bass and ince day 26every ather day.On treatment day20, the volume of diuresis was 400 mL day Oi 250 EU mL") endotoxin concentrations are associated with 100% mortality whereasthe concentrations of 50-250 EU ‘mL and 10-50 EU mi! with 75% and 158% mortality respec tively 5. Intravenous administration of an appropriate ant- biotic dose was found to eradicate meningococc fom the cerebrospinal uid after 3-4 hand to reduce the endotoxin concentration in serum by 50% after 2 hours (5). In our case, an extremely high activity of endotoxins in blood correlated with increased symptomsand pathological changes characteristic of septic shock. Elimination of endo- toxins from circulation isto support the standard therapy of sepsis caused by Gram-negative bacteria [19]. Moreover it contributes to the improvement of haemodynamic param- eters and reduced mortality (20). ‘The availableliterature contains only afew descriptions of cases.in which the Altec fiter was used to eliminate en- dotoxinsin patients wth septicshock Thefilter was applied during cardiac surgeries with extracorporeal culation 21, 22], Since endotoxins were not detected in the patients studied and they did not have symptoms of septic shock, no significant effects of endotoxin elimination on the evel, of cytokines or improved cinial conditions were demon- strated. Effective elimination of endotoains using the Alteco fiter was described in a patient with severe sepsisinduced by Gram-negative bacteria complicating peritonitis [23]. Reduced levels of endotoxins in plasma correlated with in- creased efficiency ofthe cardiovascular system. Likewise, in cour case, after two 2-hour procedures with the Alteo filter, concentations of endotoxins were found markedly lower and patients clinical condition improved. CONCLUSIONS. ‘The instant decision to transfer the patient to ICU and early identification of the type C Netsseria meningltiisanti- gen using the latex test enabled the institution of suitable antibiotic therapy. Thanks to the use of basicand advanced therapeutic methods, 12. infusion of activated protein C, continuous renal replacement therapy and elimination of endotoxins, the patient recovered from multiple organ fil- Uren the course of meningococcal shock. 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Cola Wuyteke A popelearenarise oterbern adltcardapuimonsry bypae= v=nale fertveandomizedcontled at wal eae Cardvase Thorac Sing 2010 1186-92 tndominal sep. Ata Araesthesl Scand 2008 52124-1025. ‘Corresponding auth ‘Westone Duszyriska, MD, PhD Chair and !"Departmant of Anaesthesiology and ntnie Toray Wroclaw Medical Univesity ul Borowsko 213, 50-556 Wroclaw Poland tole 48717932310 fe +4871 72323 09 ‘emai wduszynskagonet eu ecetved:28042012 ‘Accepted: 30.07.2012