CriticalIdea: March 2025

Ax QRS	Normal	Left	Right	N - W
D I	+	+	-	-
D II	+	-
AVF			+	-

Fungi

- 𝛽 Glucan + perete celular chitina

- unicelular/ micelii

Colonizare pulmonara

Aspergilius
Cnadida
Penicillium
Clavispora
Pneumocistis

Fungile reprezinta 0.1% din microbiomul intestinal

Ascomycota
Bazidiomycota

MUCORALES

- ubicuitari

- hife

- afinitate crescuta pentru fier (PTR1)

Imunocompromisi - cancer, imunoterapie, malnutritie, administrarea de voriconazol, GVHD, MV
DZ cu glicemii necontrolate
Neutropenie severa
COVID 19 nonsever + glucocorticoid
Chelator fier
trauma

- Sinuzita severa → abces cerebral

- sediu pulmonar, gastrointestinal, cutanat

- Black Skin

Colonizare → invazie tisulara → angioinvazie → +++ tromboza → necroza + diseminare

ASPERGILIUS

- trasnmitere - inhalare spori

- saprofit, oportunist

- forme:

ABPA - Aspergiloza Bronhopulmonara Alergica

CNPA - Pneumonie Cronica Necrotizanta cu Aspergilius

Aspergilom

Aspergiloza invaziva

IAPA - Influenza Associated Invasive Apergillosis

CAPA - Covid 19 Associated Pulmonary Apergillosis

- Covid 19 Associated Traheobronchittis

CPA - Chronic Pulmonary Aspergillosis

Neutropenic → angio invasive

Non-neutropenic → airway invasive

Colonizare → Invazie tisulara → Angioinvazie

Factori de risc:

- neutropenie (leucemii) → profilazie Posaconazol

- pneumoniii virale severe (covid)

- leziuni structurale pulmonare

- imunosupresoare (transplant)

Factori de risc CAPA

- supresie cale Interferon

- fact clinici: Tocilizumab + Dexa

* Klebsiella inhiba formarea de hife si biofilm de catre Aspergillius

Aspergiloza invaziva - IPA (Invasive Pulmonary Aspergollosis) / TBA (tracheobronchial aspergillosis)

- biomarker: galactomanan (BAL > ser) / amplificare ADN

- imagistic : halo/crescent sign Rx

1 semn/simptom compatibil

febra > 3 zile sub antibioterapie corecta
reaparitie febra > 48 ore de la oprirea acesteia sub antibioterapie neintrerupta
durere pleuretica
dispnee
hemoptizii

1 criteriu clinic

ulceratii traheo-bronsice
noduli
infiltrate pulmonare
abcese

1 criteriu ce tine de gazda

gripa
covid
BPOC moderat/sever
HIV CD4 < 200
cancer

1 criteriu micologic

galactomanan BAL > 1.0 ODI
galactomana ser > 0.5 ODI
culturi pozitive cu Aspergillius

CANDIDA SPP

- comensala

Candida

Albicans
Glabrata
Thropicalis
Parapsilosis
Krusei
Kefyr
Auris

- Candemie:

neutropenie
hemodializa
cvc
chirugie abdominala

Candemie = Candida izolata din hemocultura crecoltata central/periferic (FUNDICU - vena periferica)

* Candemie → tratament timp de 14 zile dupa negatire culturi

- biomarker: 1,3 𝛽Dglucagon (BDG)

ALTI FUNGI

Pneumocystis Jiravecii Pneumonia

Antifungice

POLIENE

Amfotericina B deoxycholate PK (AmB - d)

Amfotericina B lizozomala (L -AmB)

Amfotericina B Complex lipidic (ABLC)

Mecanism actiune

- legare de ergosterol

- leziuni oxidative

- stimularea celulelor fagocitare

! Se absoarbtie in tubulatura ECMO!

! Concentratii in plaman, ficat, spina!

AMB-D

- 0.7 - 1 mg/zi in 2-4 ore

- 1.5 mg/zi in PEV timp de 6 h

- activitate dependeta de concentratie

- legare ↑ de proteine plasmatice

- 𝛥t1/2 = 24 ore, per de eliminare 15 zile

- concentratie ↑ in ficat, splina, maduva, peritoneu, plaman, rinichi

- concentratie ↓ in LCR, lichidul amniotic

Ef adverse

- legat de adminsitrare - febra, HTA, frison, greata ← elibereaza IL6, IL8, TNF𝛼, MCP1, IL10

- nefrotoxicitate

- ↓ K, ↓ Mg

- ANafilaxie

- Encefalita demielininzanta

- anemie normocromica

ABLC

- 1 - 5 mg/kg/zi

- nefrootoxicitate mai scazuta

- efecte secundare - reactii legate de administrare

L-AMB

- neutropenie febrila 1 - 3 mg/kg/zi

- aspergiloza 3 - 5 mg/kg/zi

- eficacitate crescuta > Aspergilius

- 6 mg/kg/zi Cryptococus

AZOLI

Imidazoli

Miconazol
Ketoconazol
Clotrimazol

Triazoli

- tinta - Ergosterolul

- inhiba - 14𝛼Demethylase = Fungal CYP

- efecte adverse: rash, cefalee, gastro-intestinale, insuficienta hepatica, ↓ QT, defecte congenitale

1 generatie - IMIDAZOLI

Fluconazol (Diflucan)

- forma IV/OR

- excretie urinara crescuta

- timp de injumatatire crescut - o doza/zi

- obezi - cresti doza

- interactiuni medicamentoase +

Itraconazol

- piele
- forma OR

- timp de injumatatire crescut - o doza/zi

- metabolizare hepatica

- interactiuni medicamentoase +++

2 generatie - TRIAZOLI

Voriconazol (Vfend)

- forma IV/OR

- Candida auris, Candida krusei, Candida glabrata, Aspergilius fumigatus

- excretie in LCR

- metabolizare hepatica

- timp de injumatatire scazut - bid

- efecte adv: modificari oftalmologice, fotosensibilitate, toxicitate osoasa, cancer piele

- interactiuni medicamentoase +++

Posaconazol

- forma IV/OR

- Candida auris, Candida krusei, Candida glabrata, Aspergilius fumigatus, Mucorales

- timp de injumatatire crescut - o doza/zi

- excretie fecala

- metabolizare hepatica

- interactiuni medicamentoase +++

Isavuconazol (Cresemba)

- forma IV/OR

- Candida auris, Candida krusei, Candida glabrata, Aspergilius fumigatus, Mucorales

- prodrug - Isavuconazonium sulfat

- timp de injumatatire crescut - o doza/zi

- metabolizare hepatica

- interactiuni medicamentoase +++

ECHINOCANDINE

Caspofungin (Cancidas)
Micafungin
Anidulafungin (Ecalta)

- inhiba sinteza de 𝛽 1,3 D glucagon

- efecte adverse:

- legate de adminsitrare flush facial, edem, prurit, bronhospasm

- gastrointestinale, anemie, leucopenie,

- mai frecvente la Caspofungin

- teratogen

- fungicide pentru Candida

- fungistatice depeendente de doza pentru Aspergilius

- metabolizare

Caspofungin - citocromul P450
Micafungin - CYP
Anidulafungin - spontan in plasma

- penetranta minima in SNC

- eficiente in biofilm

- NU s emodifica doza pe ECMO

- EAGLE EYE EFFECT = scaderea eficacitatiila o doza mult peste MIC

ALTELE

Rezafungin

- generatia a doua de echinocandine

Ibrexafungerp

- inhiba sinteza de glucagon
- OR

Fosmanogepix

- IV/OR

- sinergic cu AmB

Olorofim

- OR
- Aspergilius

Odelconazol

- triazol inhalator

Volum lichid pleural

Formula Balik

Volum lichid pleural (ml) = Distanta masurata ecografic (mm) x 20

pH lichid pleural < 7.2 = infectie

The fluid is considered an exudate if any of the following are found and a transudate if all are absent (Light’s criteria) –ratio of pleural fluid to serum protein > 0.5, ratio of pleural fluid to serum LDH > 0.6, pleural fluid LDH > two thirds of the upper limits of normal serum value. Pleural fluid cholesterol > 55 mg/dL (1.42mmol/L)may also be a useful in distinguishing an exudate from a transudate.

Pulmonary Arterial Hypertension / Pulmonary Venous Hypertension

Parametru	PAH Pulmonary Arterial Hypertension	PVH Pulmonary Venous Hypertension
RV	↑	±↑
LA	↓	↑
RA/LA Size ratio	↑	N ( LA > RA)
Sept interatrial	Impins spre stanga	Impins spre stanga
RVOT	Frecvent	Rar
E/A	< 1	>1
Lat e'	N	↓
Lat E/e'	< 8	> 10
Ao pressure	N / ↓	N / ↑
PCWP	⋜ 15 mmHg	> 15 mmHg
PADP - PCWP	> 7 mmHg	< 5 mmHg

Rocuronium - blocare neuromusculara si reversie

Administrarea de rocuroniu

- doza de IOT calculata la IBW

0.6 mg/kg IBW (doza se scade cu 15 % pentru femei)

Monitorizare EMG

- TOF count sau PTC

- evitare administrare in ultimele 30 min ale procedurii daca este posibil

Reversie

TOF Ratio ≥ 0.4 dar < 0.9

Neostigmina 15-30 𝜇g/kg + Glicopirolat 1:5 imediat dupa neostigmina

TOF Ratio < 0.4

Sugammadex 2 mg/kg

TOF Ratio ≥ 0.9

NU este nevoie de reversie

TOF Count = 0 (PTC ≥ 1)

Sugammadex 4 mg/kg

Daca TOF ratio < 0.9 dupa reversie initiala se adminsitreaza Sugammadex

- dupa 3 minute daca reversia initiala a fost cu Sugammadex

- dupa 10 minute daca reversia initiala a fost cu Neostigmina

Antitrombotice

Antiagregante plachetare

Analogi de prostaglandina PGI2

Beraprost

Iloprost

Prostaciclina (Epoprostenol)

Treprostinil

Inhibitori ai glicoproteinei IIb/IIIa

Abciximab

Eptifibatida

Tirofiban

Inhibitori ai receptorului P2Y12

Tienopiridine

Clopidogrel

Prasugrel

Ticlopidina

Analogi nucleotidici/nucleozidici

Cangrelor

Elinogrel

Ticagrelor

Inhibitori ai ciclooxigenazei

Acid acetilsalicilic/Aspirina

Aloxiprina

Carbasalat calcic

Indobufen

Triflusal

Altele

Dipiridamol

Ditazol

Cilostazol - inhibitor de fosfodiesteraza

Vorapaxar - antagonist protease-activated receptor-1

Anticoagulante

Antagoniști ai vitaminei K

Cumarine:

Acenocumarol
Biscumacetat de etil
Dicumarol
Fenprocumona
Warfarina

1,3-indandione:

Clorindiona
Difenadiona
Fenindiona

Inhibitori ai factorului Xa

Heparina

Heparina cu greutate moleculara mica

Certoparina
Dalteparina
Enoxaparina - Clexane
Nadroparina
Reviparina
Tinzaparina

Oligozaharide

Fondaparinux
Idraparinux

Heparinoizi

Danaparoid
Dermatan sulfat
Sulodexid

Inhibitori direcți Xa:

Apixaban
Betrixaban
Edoxaban
Rivaroxaban

Inhibitori direcți de trombina (IIa)

Bivalenți

Hirudina
Bivalirudina
Desirudina
Lepirudina

Univalenți

Argatroban
Dabigatran
Efegatran
Inogatran
Melagatran
Ximelagatran

Altele

Antitrombina

Trombolitice/fibrinolitice

Activatori de plasminogen:

Alteplaza
Reteplaza
Tenecteplaza
Desmoteplaza
Urokinaza
Anistreplaza
Monteplaza
Streptokinaza

Altele

Ancrod
Brinaza
Fibrinolizina

Hidroxicobalamina

Mecanism:

- scavenging nitric oxide

- scade vasodilatatia

- catecholamine-sparing effect - scade necesarul de catelcolamine

Indicatii:

- intoxicatia cu cianuri

- hipotensiune refractara la administrarea de catecolamine

- efect antioxidant si mitocondrial

- socul vasoplegic post chirurgie cardiaca

Administrare:

- bolus 5 - 10 g in15 minute

Se poate repeta

Efecte secundare:

- colorare rosie a pielii, urinii si plasmei (temporar si fara alte efecte)

- hipertensiune (datorita vasoconstrictiei)

- interfera cu teste de laborator: HLG, creatinina, coagulare, lactat, bilirubina

MetilenBlue

Mecanism:

MetilenBlue inhiba sinteza de oxid nitric

Sinteza de oxid nitric

↓

L - Arginina → Oxid nitric

Indicatii:

- hipotensiune refractara la administrarea de catecolamine

- soc vasodilatator - reduce necesarul de vasodilatator

- imbunatateste oxigenarea - imbunatateste functia mitocondriala

Administrare:

- bolus 1.2 - 2.5 mg/kg IV

- PEV 0.25 - 0.5 mg/kg/h pentru 4 - 6 ore

Efecte secundare:

- Serotonin Sindrom

- Hemoliza (deficit G6PDH)

- Necroza tisulara (daca extravazeaza)

- Methemoglobinemia

Scor ICH

Scor ICH

- prezice mortalitatea la 30 de zile

GCS	13 - 15	0 puncte
	5 - 12	1 punct
	3 - 4	2 puncte
> 80 ani		1 punct
Volum	> 30 ml	1 punct
Hemoragie intraventiculara		1 punct
Hemoragie infratentoriala		1 punct