Introduction

Nearly all patients with Acute Pancreatitis (AP) experience abdominal pain which warrants prompt analgesia, and this is one of the main management priorities in the early management of AP (1). With some recent studies suggesting that EA might be a safe procedure and a promising therapeutic approach in AP (2,3,4), we sought to assess the benefit of EA over IV analgesia on pain control in patients of AP with moderate to severe pain. Apart from analgesia efficacy we also checked for improvement in organ failure, morbidity and mortality in patients of AP.

Aims & Methods

This study was conducted over a period of one and a half years. All consecutive patients of AP were prospectively included in the study with moderate to severe pain based on a numerical rating scale (NRS ≥4), irrespective of the severity of pancreatitis. Patients were sequentially allocated into 2 groups- Epidural Patient-controlled analgesia (PCA) group (Ropivacaine 0.2% + Fentanyl 2 mcg/ml) and Intravenous (IV) PCA group (Fentanyl 10 mcg/ml) + IV Paracetamol 1 gm Thrice daily and medications were given for a period of 5 days. In both groups, morphine was used as rescue analgesia at times when NRS ≥4. The primary objective was to assess pain control and the Secondary objectives were to assess the efficacy of epidural and IV analgesia on organ failure, morbidity and mortality in patients of AP. Standard statistical analysis was done and the comparison of quantitative variables with or without normal distribution was analysed using Independent t-test and Mann-Whitney test respectively. The Qualitative variables were analysed with the Chi-square and Fisher’s exact tests. P value <0.05 was considered statistically significant.

Results

We enrolled 36 patients with AP, 18 patients in each group. All baseline characteristics were comparable between the two groups. The mean age of subjects was 45.2 ± 13.3 years. The mean time of admission from the onset of pain in our study subjects was 2.56 ± 1.2 days. The mean number of days with adequate pain control was 3.28 ± 0.75 days in the epidural versus 3.11 ± 0.76 days in the IV group with no observed statistically significant difference (p = 0.496). Adequate pain control was achieved at day 3 in both groups as per NRS which was not statistically significant. The total Patients who required rescue analgesia were 16 (44.4%). Almost half of the patients 9 (50%) in the IV group required rescue analgesia in comparison to 7 (38.9%) in the epidural group, and the cumulative dose of rescue analgesia (morphine) required was 60 mg in the epidural group, which was lower than the dose required (76 mg) in the IV group though not statistically significant (p = 0.83). Organ failure was seen in a total of 9 (25%) patients (4 patients in the epidural versus 5 patients in the IV group). The most common observed organ failure was acute lung injury in 6 (16.7%), 3 in each group followed by acute kidney injury in 3 (8.3%) patients, 2 in IV and 1 in the epidural group (p = 1.0). The resolution of SIRS at day 3 in comparison to baseline was better in the epidural group as compared to the IV group (70% vs 27.7%) though statistically not significant (p = 0.089). There was no mortality in either group.

Conclusion

We concluded that thoracic epidural PCA and IV PCA were equally efficacious in pain control in acute pancreatitis. However, the need for rescue analgesia was lower in the thoracic epidural group than in the IV group, though statistically not significant. Moreover, thoracic epidural analgesia was safe, feasible, and showed an insignificant clinical trend towards early SIRS resolution.

References

1. Petrov MS, Yadav D. Global epidemiology and holistic prevention of pancreatitis. Nature reviews Gastroenterology & hepatology. 2019 Mar;16(3):175-84.
2. Sadowski SM, Andres A, Morel P, Schiffer E, Frossard JL, Platon A, Poletti PA, Bühler L. Epidural anesthesia improves pancreatic perfusion and decreases the severity of acute pancreatitis. World journal of gastroenterology. 2015 Nov 11;21(43):12448.
3. Tyagi A, Gupta YR, Das S, Rai G, Gupta A. Effect of segmental thoracic epidural block on pancreatitis induced organ dysfunction: a preliminary study. Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine. 2019 Feb;23(2):89.
4. Al-Leswas D, Baxter N, Lim WB, Robertson F, Ratnayake B, Samanta J, Capurso G, de-Madaria E, Drewes AM, Windsor J, Pandanaboyana S. The safety and efficacy of epidural anaesthesia in acute pancreatitis: a systematic review and meta-analysis. HPB. 2022 Dec.

Introduction

Pain in acute pancreatitis is the symptom to be treated urgently. There are currently no recommendations for analgesic management. Intravenous lidocaine has both analgesic and anti-inflammatory effects. Its use has never been evaluated for analgesia in acute pancreatitis. The aim of our study was therefore to evaluate the efficacy and safety of intravenous lidocaine in the management of acute pancreatitis resistant to level I and II analgesics.

Aims & Methods

We conducted a retrospective, monocentric study between January 2015 and December 2021. Patients visiting the emergency department for proven acute pancreatitis and presenting with pain resistant to group I and II analgesics, hospitalized in the hepato-gastroenterology department and treated with intravenous lidocaine, were included. Pain was assessed by retrospective collection of numerical pain scales (NPS) at the emergency department, and at each analgesic re-evaluation. Treatment efficacy was defined as the absence of need for a Level III analgesic (opioids).

Results

154 patients, hospitalized in our gastroenterology unit for acute pancreatitis and presenting with pain refractory to level I and II analgesics treated with intravenous lidocaine were included. Patients were predominantly male, with a median age of 48.5 years [37.0; 58.0]. The main etiology of acute pancreatitis was ethylic in 36% of cases. Acute necrotizing pancreatitis was present in 69% of patients. 44/154 patients received a bolus of opioid morphine in the emergency department before the administration of lidocaine. Lidocaine was prescribed in a continuous way at the dose of 2g/24h (intravenous administration with electric syringe). The median NPS before prescription of lidocaine was 8.0 [7.00; 9.00]. Lidocaine treatment was effective in 88.7% of patients (136/154). 1.3% of patients experienced lidocaine-related adverse events such as skin rash and dysgeusia. In univariate analysis, patients requiring intensive care or developing an acute respiratory distress syndrome were significantly more likely to fail lidocaine (respectively OR = 5.83; CI [1.69; 20.06]; p=0.01 and OR = 4.23; CI [1.44; 12.43]; p=0.009).

Conclusion

Intravenous lidocaine administration appears to be effective and safe for pain control in 89% of patients failing to level I and II analgesia. Further prospective studies are needed to confirm these results.
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Introduction

Abdominal pain is a prominent symptom in acute pancreatitis (AP) and has been linked to disease severity.

Aims & Methods

We aimed to examine associations between pain intensity and the outcome of AP and the discriminatory ability of pain intensity to predict these outcomes. For this, we conducted a post-hoc analysis using data from the PAINAP database of patients admitted with AP across 118 centres in 27 countries. Based on the pain intensity on admission using a numeric rating scale (NRS) of 0 to 10, patients were categorised as having no/mild (NRS 0-3), moderate (NRS 4-6) or severe pain (NRS 7-10). Demographic details and AP outcomes were compared across these three groups, and associations were explored using multivariable regression analyses. Finally, the influence of pain intensity on the probability of AP outcomes was assessed by calculating AUC-ROCs, sensitivity, specificity, positive/negative predictive values, and likelihood ratios.

Results

We included 1,727 patients, of whom 183 (11%) reported no/mild pain, 503 (29%) moderate pain, and 1,041 (60%) severe pain. Severe pain was associated with more severe AP (OR 1.66 (95% confidence interval (95%CI), 1.09-2.52), P=0.02), renal failure (OR 3.04 (95%CI, 1.35-6.87) and pancreatic necrosis (OR 2.37 (95%CI, 1.22-4.59), P=0.01) compared to no/mild pain. Severe pain had a low discriminatory ability for predicting outcomes of AP, with AUC-ROCs ranging from 0.53 to 0.61.The sensitivity was moderate for all outcomes, with the highest value (81% (95%CI, 72-88)) for renal failure. The specificity was lower across all outcomes, ranging from 41 to 42%. Positive predictive values were low (9-30%), whereas negative predictive values were higher (77-97%).The highest negative predictive value was observed for renal failure. Pain intensity (cutoff NRS ≥ 7) did not affect the post-test probability of outcomes compared to pre-test probability, suggesting that pain intensity alone is insufficient for evaluating prognosis in AP.

Conclusion

Pain intensity was associated with worse outcomes in AP, but the discriminatory performance of pain intensity for predicting AP outcomes was poor. Future research is warranted to refine the assessment of AP pain and clarify the underlying mechanisms. A more comprehensive understanding of pain in AP could improve its prognostic value, guide more personalised treatment strategies, and optimise pain management.

Introduction

The effect of analgesic modalities on short term outcomes in acute pancreatitis (AP) is unknown. Opioids are frequently used in AP but there are concerns regarding safety from preclinical models of AP. The aim of this study was to assess the effect of different analgesic modalities, in particular opioids, on the severity, morbidity, and mortality in hospitalized patients with AP.

Aims & Methods

This prospective cohort study recruited consecutive patients admitted with a first episode of AP from 1 April to 31 June 2022 with 1-month follow up. Data on aetiology of AP, clinical course, and analgesic treatment were collected. The primary outcome was the association between analgesic type and severity of AP. Statistical analysis was performed using univariate comparisons, multivariable regression, and mediation analysis.

Results

A total of 2,119 patients were recruited from 118 centers in 27 countries. The patients were 53 % male sex with median age of 55 years (IQR, 41-71). The most common aetiology of AP was gallstones (58%), followed by alcohol (21%). Pain duration prior to admission was >24 hours in 978 (47%) patients and <12 hours in 530 (25 %) patients. As for the first analgesic modality simple analgesics were administered in 1,456 (70%) patients and opioids were given in 521 (25%) patients. There were 1,383 (69%) patients who had opioid use at any time during admission. On univariate analysis, moderately severe/severe AP was associated with male sex, younger age, alcohol aetiology, predicted severe AP, higher pain scores, and opioid treatment (all p≤0.01). Also, on univariate analysis patients who received opioid treatment were at increased risk of severe AP, organ failure, necrosis, and longer length of admission (all p≤0.01). On multivariate analysis alcohol aetiology, predicted severity of AP and opioid treatment showed increased risk for moderately severe/severe AP (all p<0.001). Mediation analysis showed a significant direct effect of opioid use on AP severity (p<0.001).

Conclusion

This prospective multicentre study suggests that opioids have a direct effect on the severity and morbidity of AP. Further randomized controlled trials should be designed to test the safety of opioids in AP.

Introduction

Pain is the main symptom of acute pancreatitis (AP) and is usually intense. Most patients have relatively rapid pain relief, but some patients may experience more severe and long-lasting pain. Up till now, we cannot predict which patients will do worse. Early prediction of which patients will suffer the most pain would allow decisions to be made about increased analgesic treatment potency or different routes of administration.

Aims & Methods

Our main aim was to evaluate which baseline characteristics in AP are associated with pain evolution the first days of admission. For that purpose, we performed a post-hoc analysis of the international open label randomized clinical trial WATERFALL, which compared aggressive fluid therapy (20 ml/kg bolus followed by 3 ml/kg/h) versus moderate (1.5 ml/kg/h preceded by 10 ml/kg bolus only in case of hypovolemia) based on Lactated Ringer solution. The pain was assessed using the PAN-PROMISE scale (numerical scale with a range of 0 to 10, absence or maximum pain reported by the patient respectively) at baseline, 12, 24, and 48 hours. The predictive effect of 16 baseline variables (at study enrollment) on the evolution of pain was analyzed using a general linear model for repeated measures.

Results

A total of 228 patients were included out of 249 (the ones with PAN-PROMISE at 0,12,24 and 48 h). Younger age, blood leukocyte count, presence of signs or symptoms of dehydration, and active alcohol etiology were predictors of pain in the first 48 hours (p<0,05). With the combination of these variables, we obtained regression lines to predict 0-10 pain in the first 12, 24, and 48 hours. Baseline variables such as sex, smoking, body mass index, comorbidity, hematocrit, creatinine, temperature, heart rate, respiratory rate, biliary etiology, or randomization to aggressive or moderate fluid therapy did not independently predict pain intensity in the first days after AP.

Conclusion

Younger age, blood leukocyte count, presence of signs or symptoms of dehydration, and active alcohol etiology were predictors of pain in the first 48 hours.

Introduction

Acute pancreatitis is one of the most frequent and critical gastrointestinal diseases, therefore adequate management is essential to impact the prognosis of patients. Despite advances in the understanding of the pathophysiology of the disease and its complications, management remains a challenge and is mainly based on fluid resuscitation, pain management and early enteral nutrition.
Fluid resuscitation is the cornerstone of initial management, and acute pancreatitis treatment guidelines recommend early and aggressive hydration, however, evidence regarding what type of solution as well as what velocity of infusion should be used, is limited. There is not an established dose of intravenous fluids to prevent or reverse progression to multiple organ failure and reduce overload complications.

Aims & Methods

The main objective is to compare the clinical and biochemical outcomes of patients with acute pancreatitis who receive aggressive fluid resuscitation versus those who receive conservative fluid resuscitation after the first 48 hours of treatment.
195 patients were included, which were divided into two groups: 30 patients who received aggressive fluid resuscitation (more than 2.5 ml/kg/h) and 165 patients who received conservative fluid resuscitation (less than 2.5 ml/kg/h) during the first 48 hours of hospitalization. A second division of groups was performed based on 48-hour fluid balance: 129 patients who had a global fluid balance more than (>) positive 4000 ml and 66 patients who had a global fluid balance less than (<) positive 4000 ml.

Results

Patients with aggressive fluid resuscitation had a statistically significant smaller increase in C-reactive protein delta compared to conservative fluid resuscitation (+ 5.2 vs + 6.8, p 0.035) at 48 hours of treatment. Patients who had a 48-hour fluid balance > 4000 ml had a significantly greater increase in C-reactive protein delta (+ 11.46 vs + 3.94, p 0.012) compared to < 4000 ml 48-hour fluid balance, as well as longer time to start oral intake (79.36 vs 55 hrs, p 0.024) and greater requirement for loop diuretics (33.3% vs 14.8%, p 0.006).

Conclusion

Aggressive fluid resuscitation is associated with lower changes in levels of C-reactive protein delta compared to conservative fluid resuscitation, as long as patients do not have a 48-hour fluid balance greater than 4000 ml at 48 hours, because at this point the levels of delta C-reactive protein and delay in starting oral intake are greater compared to patients with a global balance less than 4000 ml, in addition to requiring loop diuretics in a higher percentage.

References

1.- Xiu‑Wei Li. et al. Comparison of clinical outcomes between aggressive and non-aggressive intravenous hydration for acute pancreatitis: a systematic review and meta-analysis. Critical Care (2023) 27:122.
2.- Crosignani et al. Intravenous fluid therapy in patients with severe acute pancreatitis admitted to the intensive care unit: a narrative review Annals of Intensive Care (2022) 12:98.
3.- Marcello Di Martino, et al. Systematic review and meta-analysis of fluid therapy protocols in acute pancreatitis: type, rate and route, HPB 2021, 23, 1629–1638.
4.- James L. Buxbaum, et al. Early Aggressive Hydration Hastens Clinical Improvement in Mild Acute Pancreatitis. Am J Gastroenterol 2017; 112:797–803.
5.- E de-Madaria et al., Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial, United European Gastroenterology Journal 2018, Vol. 6(1) 63–72.
6.- A. Aggarwal, M. Manrai, R. Kochhar. Fluid resuscitation in acute pancreatitis World J Gastroenterol 2014 December 28; 20(48): 18092-18103.
7.- S. Zhou, C. Buitrago, A. Foong et al. Comprehensive meta-analysis of randomized controlled trials of Lactated Ringer’s versus Normal Saline for acute pancreatitis Pancreatology 21 (2021) 1405-1410.