PANCREATITA ACUTA

 Boala inflamatorie acuta a

pancreasului care in forma
severa afecteaza si alte
organe/sisteme.
 Incidenta 12,4-15,9/100000 in
Europa.
 Un singur episod sau atacuri
recurente, fara insuficienta exo-
sau endocrina permanenta (≠
acutizarile P cr)
 Mortalitate 2-30% (SIRS si,
tardiv, suprainfectia necrozei)

Etiologie
 Alcoolica 40%
 Biliara 35-40% (si microlitiaza, probabil si sludge)
 Idiopatica : <30% (disfunctie de Oddi, pancreas divisum, microlitiaza?). Ex bilei duodenale
gaseste microlitiaza la 50% din cei cu PA “idiopatica” si numai ½ din acestia aveau sludge la echo
plana.

Cauze rare
 HTG >1000 mg/dl, cong sau dobandite; ! TGLI cresc moderat si in PA de alta etiologie; 1,5-4% din
cazuri; Uneori amilaza nu creste prin interferenta cu Htriglic.
 HCa 0,2-0,4%. probabil cresterile acute, pt ca e rara la cei cu HCa cronica (HPTH)
 Genetica (gena tripsinogenului cationic, SPINK1, CFTR)
 Ereditara : evol catre cronicizare cu episoade repetitive
 Medicamentoase: 0,3%; sulfamide, metronidazol, tetra, diuretice, SLZ, 5ASA, AZA, AINS, IECA.
Mecanism imunologic sau toxicitate directa (diuretice)
 Infectioase: virusi (HIV, Rujeolos, Coxsackie, VHB, CMV, VZ, HS
 Bacterii — Mycoplasma, Legionella, Leptospira, Salmonella
 Fungi — Aspergillus
 Paraziti — Toxoplasma, Cryptosporidium, Ascaris
 Vasculare: vasculite, soc, hipotensiune
 Traumatisme
 Tumori pancreatice (ADK, NIMP)
 postERCP: 3-25% din proceduri (durere si crestere de enzime, nu doar enzime); risc ˄ la cei fara
indicatie, femei, tineri
 Autoimuna: mimeaza cancerul; Hgamma, ANA, HIgG4, “carnat” la CT

PA Alcoolica
 PA; PA repetate; PCC, acutizari peste PCC
 Barbati, mai tineri, bautori “de cursa lunga”
 Sinergic cu fumatul; dar si fumatul izolat
  Mec: creste sinteza si activarea intracelulara de enzime prin sensibilizarea acinara la CK sau efect
toxic direct pe acin prin metaboliti toxici (acetaldehida)

PA Biliara
 Litiaza biliara, microlitiaza, sludge? (posibil, la cei cu sludge si fara alta explicatie)
 35-40%, fara istoric de alcoolism, femei, mai varstnice
 Mecanism: obstructia W, cu sau fara reflux biliar, cu hiperpresiune in amonte, imposibilitatea
excretiei intraductale a granulelor de zimogen, cresterea Ca liber citosolic si activarea enzimelor
pancreatice intraacinar si in spatiile interstitiale si autodigestie
 ascaridiaza biliara
 tumora ampulara sau periampulara (pancreatica, duodenala)
 diverticul periampular
 NIPM
Tehnici de explorare:
 echo de suprafata (Se 90% pt litiaza de colecist; 25-50% pt coledoc; sludge: Hecho, declive, fara
con de umbra)
 TCC: 50% pt coledoc
 ERCP 90%
 EUS: 97%
 MRCP: peste 90%

Orientarea etiologica rapida

Pe scurt
 Cauza poate fi stabilita in >3/4 cazuri (enzime, Ca, TGLI, echo)
 La cei <40 de ani cu un episod nu trebuie insistat. Daca reapare, semne de alarma sau >40 de
ani: EUS/CT sau ERCP.
 2/3 criterii: durere tipica, enzime, imagistica

Clinica
 Durere: 95%, debut brusc in epigastru, +/- irad post, intensa; 5% fara durere; sensibilitate
variabila la palpare in epigastru sau difuza, meteorism, +/- ileus, fara aparare
 Greata si varsaturi: 90%
 Icter prin compresia CBP
 In formele grave pot avea manif sistemice: dispnee, hipoxemie (colectii subdiafragm sau
pleurale, ARDS), hipotensiune, tahicardie, oligurie, confuzie
 Sangerare retroperitoneala (Cullen- echimoza periombilicala) sau Turner (flanc)
 Paniculita sau necroza subcutanata
[2/3 criterii: durere carcateristica, enzime >3xLSN, aspect radiologic tipic]

Frecventa principalelor manifestari clinice in pancreatita

Testele biochimice
 Lipaza/amilaza > 3xVN (cresc in 4-8 ore); 10%
amilaza N prin interferente; lipaza persista pana la 8-
14 zile
 Amilaza creste si in: perforatie viscer, ischemie
intestinala, (scurgerea enz in peritoneu), IR, sarcina
ectopica (cel tubare), macroamilazemie, patologia gl
salivare, ERCP
 TGP >3xVN la 24-48h; VPP 95% pt etiologia biliara, Se 48%
 BT, FAlc cresc doar in caz de obstacol coledocian persist
  Dinamica bilantului hepatic: majoritatea calculilor se elimina la 48 de ore de la aparitia PA;
probabilitatea unui calcul rezidual este nula daca bilantul hepatic se normalizeaza sau se
injumatateste la 24 de ore de la debut si este de 50% daca analizele de bilant nu se injumatatesc
sau cresc

Alte teste paraclinice

 Mediatori ai inflamatiei (PCR, VSH, trombocitoza)
 ^L, ^Ht, ^ureei prin deshidratare; Hglicemie, creatinina, electrolitii
 HCa, HTGLI in functie de etiologie

Imagistica
 Edem
 Necroza: lipsa intaririi dupa administrare de contrast iv
 Inflamatia grasimii peripancreatice (aspect de pieptane)
 Colectii localizate sau nu
 Tumori, calculi
 Ansa santinela, revarsat pleural
 Echo: sensibilitate si mai redusa pt litiaza in atac (meteorism); poate fi repetata; Se 90% lit bil;
25-50% lit coledociana; nu distinge tes necrotic de cel viabil. Edem, colectii, calcificari
 ColangioRM: Se >90% lit coledoc.
 Echoendo: F sensibila pentru leziuni mici. (Se 97% lit coledoc, tumori neuroendocrine) dar
invaziva (permite si FNA). Cea mai buna pt bilant de rezecabilitate al ADK vs invazia vasculara
 TC cu contrast si protocol pancreatic: linia a II-a, Se 50% lit coledoc., preferabil dupa 48 de ore;
se poate repeta saptamanal sau in caz de manif clinice suspecte (bule de gaz)
 ERCP: nu diagnostic, doar terapeutic (risc de pancreatita 5%)
 Rgf abd simpla: calcificari (P cr), rar calculi biliari radioopaci

 Pancreatita edematoasa: marire de volum prin edem, intarire discreta, difuza (rar localizata) a
parenchimului pancreatic; grasimea peripancreatica are un aspect cetos sau de “pieptene” ca
urmare a modif inflamatorii; poate exista fluid peripancreatic
 Pancreatita necrotizanta presupune necroza tes peripancreatic si a celui pancreatic, mai rar doar
a celui peripancreatic si f rar doar a celui pancreatic. Imaginea necrozei poate fi confundata in
primele zile cu lipsa de intarire data de tulb de perfuzie. Dupa o sapt de la debutul durerii, lipsa
intaririi inseamna necroza!

Diagnostic diferential
 Ulcer peptic
 Colica biliara, colecistita acuta, colangita acuta
 Perforatia viscerala
 Ischemia mezenterica

Istoria naturala
 90% PA usoara (edematoasa/interstitiala): mortalitate 3%, fara necroze, fara insuf de
organ/complicatii locale/sistemice
  5-10% PA severa (necrotica): mortalitate 15-20%, insuficienta de organ persistenta
 PA moderata: insuf de organ temporara si/sau complicatii locale sau sistemice; severitate
intermediara
 Vindecare fara sechele sau cu complicatii
 Episod unic, recurente sau cronicizare (mai ales cea etilica)

Complicatii locale
 Pseudochist (colectie fluida, incapsulata, apare la >4-6 saptamani )
 colectie lichida peripancreatica (in primele 4 saptamani, colectie omogena, fara perete,
adiacenta pancreasului, fara necroze),
 colectie necrotica (colectie heterogena- fluid si tes necrozat, fara perete, intra- sau
extrapancreatica)
 necroza incapsulata (colectie heterogena cu perete inflamator, intra- sau extrapancr)

Alte complicatii locale

 Ruptura de duct pancreatic (ascita, pseudochist)
 Icter prin compresia CBP
 Tulburari de evacuare gastrica
 Tromboza de vena splenica sau porta
 Necroza colonica
Reaparitia simptomatologiei sau cresterea secundara a enzimelor pancreatice sau semnele sistemice de
infectie (febra, leucocitoza- la mai mult de o saptamana) sugereaza o complicatie locala

Complicatii sistemice
 SIRS,
 Ileus localizat sau generalizat (ansa santinela)
 Soc (hipovolemic, hemoragic); petele Turner (flanc) si Cullen
 MSOF: Insuf respiratorie: hipoxemie, paO2 60mmHg; Insuf renala acuta: hipovolemie, CID
 Pleurezie/ascita (bogate in amilaza)
 hipoCa-emie <2mmol/L; rar tetanie, hipo/hiperglicemie
 Exacerbarea unei suferinte preexistente (BCI, BPOC)
 Tromboze venoase la distanta

[Algoritm dg: crt clinicobiologice si echo de suprafata; daca TA si echo sunt N etiologia biliara nu e
exclusa; urmarire cu TA si cu BT: daca cresc ERCP; daca nu cresc, la o luna EUS sau cholangioRM.
Daca litiaza coledociana e documentata echo/CT sau daca are si colangita sau daca e icteric, siguranta dg
e suficienta si se face direct ERCP.
Daca are litiaza veziculara si/sau crestere de TA, fara icter sau colangita, iar PA e severa, se face in
primele 72 de ore ERCP; daca PA e usoara, se face intai EUS.
Dupa un episod de PA biliara, in aceeasi internare colecistectomie si colangiografie. ERCP daca are litiaza
coledociana dupa chirurgie.]
Evaluarea severitatii “Este foarte dificil sa faci predictii, mai ales daca ele sunt despre viitor” Niels Bohr
Pentru prognostic, alegerea terapiei si a locului de internare
 Criterii clinice
 Markeri ai inflamatiei
 Scoruri clinicobiologice: Ranson, Glasgow, APACHE II
 Scorul CT Balthazar

Evolutie
Stratificarea pacientilor dupa severitatea atacului este imperioasa!
 Semnele clinice si simpt (diureze, TA, AV, SaO2, starea constientei, etc) sunt predictive doar pt
50% din pacienti deci trebuie asociate unor masuratori obiective.
 BMI >30 (grasimea este un substrat pt enz pancr activate si sursa de mediatori ai inflamatiei);
risc > de SIRS sau de complicatii locale, dar nu influenteaza mortalitatea
 Varsta > 70 de ani: progn mai prost; Se= 55%; Sp= 88%
 PCR > 150 mg/l la 48 de ore: progn nefavorabil. Se 40%, Sp 100%, VPP 67%
 Procalcitonina: Se > dar Sp < (infectie?). Se 93%, Sp 88%, VPP 75%.
 Toate variabilele individuale au VPN aprox 100%.

Scorurile prognostice
 Scorurile sunt utile pentru alegerea strategiei terapeutice.
  Atlanta
 Ranson: cel mai cunoscut, dar greoi: la internare si la 48 de ore. Se 65%; Sp 70% PAS> 2 pct;
Ranson < 3 pct are M 0, iar > 6 M 50%.
 APACHE (acute physiology and chronic health evaluation) II: Se 65-80%; Sp 70-90%; PAS> 7 pct;
si mai complex, dar calculabil instantaneu daca ai acces la un calculator.
 Pentru ambele scoruri PPV 25-70%
 Nevoie de scoruri simple; SIRS

TRATAMENT: MASURI GENERALE IN PA USOARA

 Repausul alimentar nu este necesar; daca se poate alimenta, dieta saraca in grasimi la inceput;
daca nu poate, glu 5% pentru hidratare este suficienta 48 de ore; Tub enteral doar daca nu se
poate alimenta oral > 7 zile
 Calmarea durerii: paracetamol, opioide (evit. Morfina/codeina)

[Management : 4. Evaluate Response to Initial Therapy Patients that respond appropriately to initial
resuscitation efforts should continue to receive supportive care. However, patients with persistent pain,
fever, SIRS, or evidence of organ dysfunction (partial pressure of oxygen _60 mm Hg, oxygen saturation
_90%, systolic blood pressure _90 mm Hg, creatinine _2.0 g/dL) after 72 hours should have a rapid-bolus
contrast-enhanced CT scan to evaluate for necrosis. These patients should be considered for transfer to
an intensive care unit and/or a specialty care center (AGA, ACG, UK, JPN). Additional evaluation should
also include a thorough investigation for potential sources of extra-pancreatic infection including chest
radiography, urine, and blood cultures. Patients with persistent organ failure require additional
monitoring to ensure adequate intravascular volume resuscitation. Use of central venous pressure (CVP)
measurement via a centrally placed catheter is most commonly used to determine volume status in this
clinical setting. However, recent data indicate that the intrathoracic blood volume index (ITBI) may have
a better correlation with cardiac index than central venous pressure, allowing more accurate assessment
of volume status for patients managed in the ICU. There is evidence in the form of randomized
controlled trials and meta-analysis to support a beneficial role for enteral nutrition compared with total
parenteral nutrition (TPN) in severe acute pancreatitis. Specifically, enteral nutrition via nasojejunal
feeding has been associated with reduction in infectious complications and length-of-stay when
compared with total parenteral nutrition. Most guidelines recommend initiation of enteral nutrition if
the patient is likely to remain NPO for greater than 5–7 days (AGA, ACG, UK). In practice, this
determination can be difficult. Patients with refractory pain, persistent SIRS, or organ dysfunction after
48 hours should strongly be considered for initiation of enteral nutrition. A multicenter randomized
controlled trial sponsored by the National Institutes of Health is currently underway to determine the
optimal route of enteral nutrition in severe acute pancreatitis (nasojejunal versus nasogastric
alimentation).]

MASURI GENERALE IN PA MODERATA /SEVERA

 Necesar energetic crescut inca din primele ore! “Early refeeding”; translocatia
 Alim per os, initial dieta clara; aspiratie pe tub doar daca varsa
 Alim. enterala pe tub nasogastric/jejunal in primele 48 de ore daca nu poate oral
 Alim parenterala totala, doar daca nu se poate enteral sau daca nu putem asigura necesarul
caloric.
 Pierd fluide in spatiul 3; reechilibrare HE iv/cateter central, agresiv in cazuri severe: 4-5l/24h,
cristaloide si coloide (2:1); orientare dupa diureza (0,5 ml/kc/h)/PVC. Atentie la EPA!
 Calmarea durerii
 Transfuzii la Ht<30%
 Antibiotice (imipenem) doar daca exista dovezi de infectie (febra in primele zile e consecinta
inflamatiei sterile). Altminteri nu aduc beneficii, ci cresc riscul suprainf fungice
 Antienzimele, antiTNF, antagonistii activarii plachetare, lavajul peritoneal, antisecretoriile:
inutile
 Anticoagulare cu heparina

TRATAMENT SPECIFIC
 ERCP urgent (<72 de ore) in caz de colangita asociata/ PA biliara severa
 Indometacin/diclofenac supozitor post ERCP/ stent pancreatic temporar
 Colecistectomie rapid (in aceeasi internare, < 2sapt), dar “la rece” (dupa depasirea atacului)
 ERCP electiva, cu sfincterotomie, pt diskinezie de Oddi sau tumora
 Drenajul colectiilor peripancreatice: endoscopic, rx interv, chir
 Abstinenta de la b alcoolice, fumat
TRATAMENTUL COMPLICATIILOR
PSEUDOCHISTURILE:
 <5% din pancreatitele acute
 Fara legatura cu severitatea atacului
 Durere si crestere enz persistenta
 50% se palpeaza ca o masa
 Echo/CT dg si monitorizare
 Cele <6 cm se resorb in 6 saptamani;
 Daca continua sa cresca dupa 6 sapt sau sunt simptomatice, drenaj endoscopic (EUS,
transpapilar sau transgastric), radiologic sau chir (daca are varice gastrice, duodenale, la peste 1
cm de peretele digestiv sau susp de neoplasm chistic)

INFECTIA TESUTULUI NECROTIC

 De obicei dupa >7 zile: imagistica (bule de gaz in tes pancreatic/peripancreatic – extraluminal),
clinica (febra, frison, leucocitoza)
 Antibiotice, drenaj radiologic, endoscopic, chirurgical
 Monitorizare imagistica

[Management of Early Complications (First 2 Weeks of Hospitalization) Diagnosis of necrosis. The most
accurate study for diagnosis of necrosis remains rapid bolus contrast-enhanced abdominal CT. Current
recommendations are to obtain a CT scan for evaluation of necrosis in a patient with evidence of
ongoing pain, fever, persistent SIRS, or organ dysfunction after 72 hours of illness (AGA, ACR). In
addition to necrosis, a CT scan can help identify further complications such as acute fluid collections,
pleural effusion, or ascites. Whether the extent of necrosis correlates with disease severity is
controversial.
 Role of prophylactic antibiotics. Guidelines are equivocal on the use of prophylactic antibiotics
(AGA, ACG, UK, JPN). Two recent randomized double-blind, placebo-controlled trials failed to
demonstrate any benefit of prophylactic antibiotics for prevention of infection in necrotizing
pancreatitis. An additional meta-analysis demonstrated that higher quality studies were less
likely to demonstrate a benefit for prophylactic antibiotics. Overall, there is little evidence to
support use
 of prophylactic antibiotics for the prevention of infected necrosis.
 Treatment of infected necrosis. A CT-guided fine needle aspiration of necrosis is useful in the
diagnosis of infected
 necrosis (AGA, ACG, Society of Surgery of the Alimentary Tract). This approach has been
demonstrated to be safe and
 accurate for the detection of pancreatic infection. It is reasonable to start antibiotics in a febrile
patient after appropriate cultures have been obtained. If cultures return negative, antibiotics
should then be discontinued. Overall, rates of infected necrosis have been in decline over the
past several decades, from 30%–32% in reports from the 1990s to 9%–12% in more recently
published trials. Management of infected necrosis remains surgical debridement, although there
is now greater experience with usage of percutaneously-placed drainage catheters in unstable
patients as a temporizing maneuver until surgical debridement can be safely performed.
 Impact of extrapancreatic (hospital-acquired) infection.Two large, multicenter studies have
recently called attention to the impact of extrapancreatic infection in acute pancreatitis. In a
study from the Netherlands, more than 25% of patients with acute pancreatitis developed either
bacteremia or pneumonia during their hospitalization. The majority of these infections occurred
within the first 2 weeks. By contrast, infected necrosis occurred on average 4 weeks after
presentation.
 In a separate cohort study involving 177 United States hospitals,we determined that hospital-
acquired, extrapancreatic infection was associated with greater than a 2-fold increased risk of
mortality even after adjusting for disease severity. The clinical implication of these findings is
that an extensive evaluation for potential sources of extrapancreatic infection should be
undertaken and if detected, these infections should be treated aggressively.
 Management of organ failure. Respiratory failure is the most common form of organ
dysfunction in acute pancreatitis Circulatory shock and renal insufficiency are also observed in
severe cases. Although various measures of organ failure exist, the majority of
recommendations define respiratory
 compromise as a room air oxygen saturation _90%, a systolic blood pressure _90 mm Hg, or a
serum creatinine _2.0g/dL after initial fluid resuscitation. Up to 20% of patients may have
evidence of persistent organ failure 48 hours into their hospitalization. Patients with multiorgan
dysfunction are at the greatest risk for mortality and specialty care referral is strongly
recommended for these patients (AGA, ACG, UK, JPN).
 Areas of Uncertainty
 Fluid Resuscitation
 Currently there is no evidence available from prospective controlled trials to support
recommendations for aggressive fluid resuscitation for preventing complications in acute
pancreatitis. The optimal rate, type, and volume of fluid for initial resuscitation remain unclear.
At present, there are 2 active multicenter randomized clinical trials registered at Clinicaltrials.
gov that focus on fluid resuscitation in acute pancreatitis.Our study, the Trial of Intravenous,
Goal-directed Early fluid Resuscitation (TIGER) seeks to compare a targeted approach to
resuscitation that utilizes early changes in BUN to direct resuscitation parameters. A concurrent
study in Germany (EAGLE) is evaluating targeted fluid resuscitation in the critical care setting
utilizing a proprietary system of hemodynamic monitoring (PiCCO, Pulsion Medical Systems AG,
Munich,Germany).
 Analgesia
 The optimal method of delivering analgesia to patients with acute pancreatitis has yet to be
established. International guidelines vary widely regarding recommendations for both types of
analgesic medication as well as dosing regimens. Further prospective studies are needed to help
determine which
 regimens are most effective at achieving rapid and durable pain relief. The World Health
Organization has recommended a stepwise approach to pain control in cancer that may have
some applicability in acute pancreatitis.
 Anti-Inflammatory Therapy
 The role of anti-inflammatory therapy remains uncertain. Currently, Japanese guidelines call for
use of protease inhibitors despite marginal evidence from clinical trials and meta-analysis.
Previous investigations evaluating the impact of platelet activating factor inhibitor (lexipafant)
 and interleuken (IL)-10 have not demonstrated benefit. Although numerous candidate anti-
inflammatory agents have demonstrated benefit in experimental models of acute pancreatitis,
none have proven beneficial in human disease.
 Prevention of Hospital-Acquired Infection
 There is a high incidence of extrapancreatic, hospitalacquired infection in acute pancreatitis.
These infections can have substantial impact on outcome. It remains to be determined whether
aggressive infection control measures can help reduce the rate of hospital-acquired infection in
acute pancreatitis.
 Certainly, in patients with ongoing systemic inflammation or evidence of clinical deterioration, a
thorough investigation for extrapancreatic infection is warranted.
 Impact of Specialty Care
 Several guidelines including those from the UK and Japan recommend a specialist team
dedicated to the treatment of acute pancreatitis. Other guidelines recommend consideration of
transfer to a hospital with specialty care services in the case of severe forms of acute
pancreatitis. It remains to be determined which patients benefit from specialty care and at what
stage of illness. In this era of cost containment, it may be worthwhile to consider the opposite as
well. For example, not all patients may require the added expertise and expense associated with
treatment in a tertiary referral center. A recent scoring system (Harmless) was eveloped to
identify patients likely to have mild disease that might be appropriately triaged to an
observation unit.]