Table 1.

Animal studies focusing on the role of thoracic epidural analgesia in acute pancreatitis

First author and reference	Year	Subjects	Number	Groups	Epidural analgesia	Main measures	Findings	Comments
Demirag [23]	2006	Rats	19	Three groups:  1) AP [9]  2) TEA [4]  3) AP + TEA [6]	Catheter positioned between T7 and T9. Bupivacaine 0.4 % 20 μl/h	Hemodynamic and biological parameters Arterial blood gases Laser Doppler flowmetry of pancreatic microcirculation Histopathological analysis	- TEA induced a strong increase in pancreatic microcirculation compared with AP group - TEA reduced the severity of metabolic acidosis - Histopathological analysis showed that TEA reduced acinar cells, without reaching statistical evidence	Three different groups Histological analysis Reproducibility of the procedure
Lauer [24]	2007	Rats	21	Three groups:  1) AP [7]  2) AP + TEA [7]  3) Shama + TEA [7]	Catheter insertion in L3– L4, advanced to T6. Bupivacaine 0.5 % 15 μl/h	In-vivo and in-vitro analysis Hemodynamic and biological parameters Arterial blood gases Receptor-independent vasoconstriction Receptor-dependent and independent vasoconstriction by angiotensin and bradykinin	- AP group had more severe metabolic and lactate acidosis compared with rats benefitting from TEA - TEA induced a better arterial oxygenation and higher mean arterial pressure compared with AP - TEA induced a better hypoxic vasoconstriction response associated with a reduction of exhaled nitric oxide, showing less smooth muscle cell dysfunction compared with AP - TEA induced a better receptor sensitivity to angiotensin II and bradykinin compared with AP	Three different groups In-vivo and in-vitro analysis Reproducibility of the procedure
Freise [26]	2009	Rats	28 + 22	Four groups:  1) Shama + NaCl [7]  2) Shama + TEA (7 + 8)  3) AP + NaCl (7 + 7) 4) AP + TEA (7 + 7)	Catheter insertion in L3– L4, advanced to T6. Bupivacaine 0.5 % 15 μl/h	Hemodynamic and biological parameters Arterial blood gases Intravital microscopy for sinusoid perfusion and diameter FasL expression measures Histopathological analysis	- TEA reduced overall apoptosis and hepatocyte apoptosis compared with AP - TEA prevented sinusoid vasoconstriction, but did not influence loss of sinusoids and sinusoidal perfusion compared with AP - TEA did not induce significant changes in hemodynamic parameters, FasL expression, and arterial blood gases	Four different groups Blinded investigators and pathologist  Large sample with 22 rats added for histopathological analysis and FasL measures Reproducibility of the procedure
Freise [18]	2006	Rats	28	Four groups:   1) Shama + NaCl [7]   2) AP + NaCl [7]   3) AP + TEA [7]   4) AP + TEA 7 hours after AP induction	Catheter insertion in L3– L4, advanced to T6. Bupivacaine 0.5 % 15 μl/h	Intravital microscopy of ileal mucosa Hemodynamic and biological parameters Arterial blood gases Histopathological analysis	- TEA increased survival at 7 days from 33 to 73 % compared with AP group - TEA did not induce more hypotension compared with AP group - A reduction of 50 % of the ileal arteriolar perfusion was observed in the AP group, restored to normal in the AP + TEA and in delayed TEA groups - TEA reduced lactate concentration in the AP + TEA and delayed TEA group compared with AP - TEA reduced histologic injury compared with AP alone, without reaching statistical evidence - TEA induced a diminution of IL-6 plasmatic concentration compared with AP	7 days of follow-up Data on mortality Four different groups, one with delayed TEA, closer to clinical situation  Blinding of investigators and pathologists Reproducibility of the procedure
Bachmann [27]	2013	Pigs	34	Two groups:   1) AP + TEA [13]   2) AP alone [21]	Catheter positioned between T7 and T8. Bupivacaine 0.5 % bolus + continuous 4 ml/h	Hemodynamic and biological parameters, arterial blood gases  Laser Doppler flow measures of pancreas microcirculation All of the experiment was realized in ICU settings with hemodynamic monitoring and automated infusion system	- TEA improved overall survival at 7 days, from 29 % in AP group to 82 % in the group receiving TEA - TEA improved microcirculation and tissue oxygenation of the pancreas - TEA reduced histopathological pancreatic lesion compared with AP	7 days of follow-up Data on mortality Experiment on big animals, allowing controlled hemodynamic conditions such as in ICU settings Verification of TEA spread by epidurogram Blinded pathologist Reproducibility of the procedure

^aSham defines a group with no induction of acute pancreatitis

TEA thoracic epidural analgesia, AP acute pancreatitis, FasL Fas ligand, IL interleukin