Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• In the NSABP B-27 trial:
  • 2411 women with operable breast cancer were randomly assigned to receive:
    • Preoperative:
      • Group 1:
        • AC followed by surgery
      • Group 2:
        • AC followed by docetaxel then surgery
      • Group 3:
        • AC followed by surgery and then docetaxel
    • Tamoxifen:
      • Was initiated concurrently with chemotherapy
  • The addition of docetaxel:
    • Preoperatively or postoperatively:
      • Did not significantly improve OS or DFS
    • The sample size of the study was deemed insufficient to yield significance for the moderate improved DFS:
      • However, in the subset of patients with a clinical partial response to AC:
        • The addition of preoperative docetaxel (but not postoperative docetaxel):
          • Resulted in a significant increase in DFS compared with AC alone:
            • Hazard ratio, 0.71; 95% confidence interval, 0.55–0.91; P=.007
        • There was a significant decrease in the cumulative incidence of all local recurrence as first events in the two groups treated with docetaxel:
          • Approximately half of which was accounted for by ipsilateral breast tumor recurrences in women treated with breast-conserving therapy
• For protocol B-27:
  • Mean tumor size was 4.5 cm:
    • This and other key characteristics were evenly balanced among the three treatment arms
  • The addition of docetaxel preoperatively resulted:
    • In significant increases in cCR and pCR at the time of surgery compared with AC alone:
      • 63.6% versus 40.1% and 26.1% versus 13.7%, respectively
    • Despite this:
      • Addition of docetaxel to AC:
        • Did not significantly impact:
          • On survival in this cohort of patients
        • There was a trend toward improved DFS in group II patients who received preoperative docetaxel (T):
          • But this was not statistically significant:
            • 72% versus 67% DFS at 5 years; HR = 0.86, P = 0.10
        • In an analysis of relapse-free survival (RFS):
          • Which did not include second primary cancers:
            • Group II had a significantly better outcome compared with group I:
              • 74% versus 69% RFS at 5 years; HR = 0.81, P = 0.03).
            • Group III RFS was not significantly different from group I:
              • 71% at 5 years; HR = 0.91, P = 0.32
        • Addition of docetaxel:
          • Significantly reduced the incidence of local recurrences as first events:
            • Including IBTR in patients treated with breast conservation
    • There were no significant interactions between treatment and estrogen receptor status, age, tumor size, or clinical nodal status
    • An exploratory analysis of treatment effects in subsets of patients according to clinical response to AC suggests that:
      • Preoperative T, but not postoperative T:
        • Significantly increased DFS in patients who had a partial clinical response after four cycles of AC:
          • 63%, 74%, 65% at 5 years for groups I, II, and III
            • HR = 0.68 for group II versus group I, P = 0.003
      • Addition of T:
        • Did not appear to be beneficial in patients:
          • Who were nonresponders after AC nor in those patients who had a cCR after AC
      • Pathologic complete response:
        • Was a highly significant predictor of DFS and OS in all treatment groups (HR = 0.45, P < 0.0001, and HR = 0.33, P < 0.0001, respectively)
      • In addition, pathologic nodal status after chemotherapy was a significant prognostic factor for survival:
        • Independent of pathologic response in the breast

REFERENCES

1. Bear HD, Anderson S, Smith RE. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019-2027.
2. NSABP Clinical Trials Overview. Protocol B-27. A Randomized Trial Comparing Preoperative Doxorubicin (Adriamycin) Cyclophosphamide (AC) to Preoperative AC Followed by Preoperative Docetaxel (Taxotere) and to Preoperative AC followed by Postoperative Docetaxel in Patients with Operable Carcinoma of the Breast. http://www.nsabp.pitt.edu/B-27.asp. Accessed December 18, 2016.

#Arrangoiz #Surgeon #BreastSurgeon #CancerSurgeon #BreastCancer

👉Mammograms help women find breast cancer early, often when a tumor is still too tiny to feel and treatment may be easier.

👉These low-dose X-rays are available in two forms: 2D and 3D.

👉With 3D mammography becoming more widely available, many women aren’t sure what the differences are between the two options. Here are five things to know about the similarities and differences between 2D and 3D mammograms:

2. Both 2D and 3D mammograms collect images of the breast, but in different ways: During a 2D mammogram (also called conventional digital mammography), two pictures are typically taken of each breast—one from the side and one from above.
   During a 3D mammogram (also known as digital breast tomosynthesis), multiple images are taken of the breast from different angles. A computer combines the images to create a 3D picture of the breast, which may give doctors a clearer view of the breast tissue.
   
3. Compression of the breasts is the same for both types of mammogram:During both 2D and 3D mammograms, your breasts will be placed on a special platform and gradually compressed with a clear paddle. Compression is necessary in order to get the best images.
   
4. 3D mammograms may have some advantages over 2D mammograms: Among their potential benefits, 3D mammograms may:
   • Improve the ability of doctors to accurately diagnose breast cancer.
   • Find small tumors that may have remained hidden on a 2D mammogram.
   • Provide clearer images of abnormalities in dense breasts. Women who have dense breasts—defined as breasts that have a lot of glandular tissue and not a lot of fat—are at slightly higher risk of developing breast cancer.
   • Reduce the number of times women are called back for further testing because of false alarms.
     
5. The American Cancer Society (ACS) doesn’t recommend one type of mammogram over the other: So far, the ACS is neutral about its recommendations regarding 3D mammograms.
   
6. Where you get your mammogram matters: While all radiologists are trained to read mammograms, some are more highly trained than others to interpret their results.
   

#Arrangoiz #BreastSurgeon

• The NSABP B-51 / RTOG 1304 trial:
  • Is a phase III randomized clinical trial currently accruing patients
  • That is designed to evaluate the role of regional nodal radiotherapy (RT):
    • In patients who had documented positive axillary lymph nodes prior to undergoing NAC:
      • Who subsequently convert to pathologically negative axillary nodes after the administration of NAC
  • The primary endpoint:
    • Is to determine if regional nodal RT:
      • Significantly reduces the rate of in-breast cancer recurrence free interval
  • Node positivity:
    • Will be documented by either FNA or core needle biopsy:
      • Prior to the administration of NAC
  • Patients will undergo standard NAC with the addition of anti-HER2 therapy for patients with HER2-positive tumors
  • Patients can have either mastectomy or breast-conserving therapy:
    • Mastectomy patients will be randomized to:
      • Either no RT or regional nodal RT and chest wall RT
    • Breast conservation patients will be randomized to either:
      • Whole-breast RT or whole-breast RT plus regional nodal RT

REFERENCES

1. NSABP Clinical Trials Overview. http://www.nsabp.pitt.edu/B-27.asp. Accessed February 4, 2017.
2. RTOG foundation INC. https://www.rtog.org/ClinicalTrials/ProtocolTable/StudyDetails.aspx?study=1304. Accessed March 22, 2017

#Arrangoiz #BreastSurgeon #CancerSurgeon #BreastCancer

• Acute Respiratory Distress Syndrome (ARDS):
  • Is a condition of diffuse alveolar damage and inflammation:
    • Secondary to any number of possible processes
  • While ARDS always causes hypoxemia:
    • Not all hypoxemia is ARDS
  • ARDS:
    • Is the most common severe complication of COVID-19:
      • Contributing to the severe morbidity and mortality of the infection
• ARDS is defined by four criteria:
  • The condition must be acute:
    • Less than 7 days:
  • The findings are not solely explained by cardiogenic pulmonary edema
  • The chest X-ray must have bilateral opacities
  • While on at least 5 cmH2O of positive pressure ventilation:
    • The ratio of PaO2 to FiO2 (expressed as a decimal, such as 0.7):
      • Must be less than 300
    • Mild ARDS is a:
      • PaO2/FiO2 ratio of 200 to 300
    • Moderate ARDS is:
      • PaO2/FiO2 ratio 100 to 199
    • Severe ARDS is:
      • PaO2/FiO2 ratio < 100
• Positive pressure ventilation:
  • Especially with large tidal volumes or high pressures:
    • Has been shown to cause injury in both patients with:
      • ARDS as well as patients who do not yet have ARDS
    • Of all the interventions in critical care, few have been as reproducibly beneficial to patients as:
      • Low tidal volume ventilation
• Many of the maneuvers used in severe hypoxemia to improve oxygenation and ventilation:
  • Can be deleterious in the long term
• Increasing the mean airway pressure (MAP):
  • Is one of the major goals of positive pressure ventilation:
    • Higher MAPs are often associated with improved oxygenation
• The factors that increase MAP:
  • Are those that either:
    • Increase the pressure in the airways such as:
      • Tidal volume
      • PEEP
      • AutoPEEP
    • Increase the amount of time the positive pressure is delivered:
      • Such as the inspiratory time
• However:
  • Despite short-term improvement in oxygenation:
    • High pressures in the alveoli are also associated with worse long-term outcomes:
      • Therefore, the clinician has to balance the risk of increasing the MAP with using good, evidence-based ventilator management
• Tidal volumes:
  • Are best represented in both mLs and mLs/kg of predicted body weight:
    • The predicted body weight is a surrogate for the patient’s anticipated lung volume:
      • Lung volumes depend upon a patient’s:
        • Height and biological sex
      • Actual body weight should never be used as a replacement for the predicted body weight
  • Once the initial tidal volume is selected, the pressures should be assessed:
    • In ARDS, as well as other patients:
      • Maintaining a Pplat < 30cm H2O:
        • Is key to preventing ventilator-induced lung injury:
          • Note that the Pplat will be determined by:
            • The tidal volume given and
            • The compliance of the respiratory system
    • ARDS usually results in decreased compliance:
      • Resulting in stiff lungs
    • Interestingly, in patients with COVID19:
      • Their compliance seems to be higher than other patients with comparable ARDS
• Using an inspiratory hold:
  • The Pplat should be confirmed:
    • To be less than 30 cm H20
  • If Pplat is > 30 cm H20:
    • A lower tidal volume should be initiated:
      • Even down to 4ml/kg
• PEEP is the next setting to address:
  • Clearly:
    • Oxygenation is a critical factor for these patients
  • PEEP:
    • Increases the mean airway pressure (MAP) and thereby:
      • Improves oxygenation
  • PEEP additionally can help:
    • Prevent further derecruitment
  • A physiologic goal in setting PEEP is:
    • To prevent atelectasis without extending into overdistention
• Many of these patients will need moderate to high PEEPs of 8 to 16 cmH2O, and at times, even greater
• The PEEP may contribute to the Pplat, and therefore:
  • The Pplat should be checked with any PEEP change, just as with any TV change
• The time when an increase in PEEP will not, or will only minimally, increase the Pplat is:
  • When the patient is derecruited and increasing the PEEP helps recruit collapsed lung:
    • In this instance, the increase in PEEP can actually improve compliance, and therefore not increase the Pplat
• This is the principle behind performing a recruitment maneuver and a “BestPEEP” trial to find a PEEP that optimizes compliance:
  • Preventing both atelectasis and overdistention.

• Driving pressure (∆P):
  • Is the term that describes the pressure changes that occur during inspiration, and:
    • Is equal to the difference between the plateau pressure and PEEP:
      • Pplat – PEEP:
        • For example, a patient with a Pplat of 30 cmH2O and a PEEP of 10 cmH20 would have a driving pressure of 20 cmH2O:
          • In other words, 20 cmH2O would be the pressure that extered to expand the lungs:
            • Studies have shown that a driving pressure of < 15 cmH2O:
              • Is associated with better outcomes in patients with ARDS
• While most patients will be started on a FiO2 of 100%, especially if hypoxemic:
  • The FiO2 should be decreased as tolerated after checking an ABG (arterial blood gas)
  • Oxygen toxicity is increasingly appreciated in numerous conditions:
    • As decreasing the FiO2 as much as is safely tolerated is appropriate
  • A reasonable target is:
    • An SpO2 of 92% to 96%
• An ABG (arterial blood gas) provides important information:
  • Allowing the clinician to calculate:
    • The PaO2 to FiO2 (P/F) ratio, and thereby categorize the severity of the patient’s ARDS
• Patients being ventilated with low tidal volumes:
  • Will require a higher rate:
    • To maintain minute ventilation
      • Minute ventilation = TV + RR
  • Most patients with ARDS:
    • Will require RR of 20 breaths per minute or greater:
      • This is especially important to consider as many patients with ARDS will be hypermetabolic:
        • With increased CO2 production
• Initial Ventilator Settings in ARDS:
  • Tidal Volume:
    • 4 to 8 ml/kg PBW:
      • Starting with 6 ml/kg
  • Respiratory Rate Higher:
    • Often > 20 breaths per minute
  • PEEP ≥ 8 cmH2O:
    • Avoiding overdistention
  • FiO2 Decrease as tolerated:
    • SpO2 ≥ 92%
• Severe Hypoxemia:
  • At times, patients may have refractory, severe hypoxemic respiratory failure:
    • After checking all ventilator settings as described above:
      • The clinician should employ additional evidence-based maneuvers
  • At times, a patient may be well sedated yet dyssynchronous with the ventilator:
    • Ventilator dyssynchrony:
      • Is associated with worse outcomes and should be avoided
      • A recent trial, published in 2019, did not find improved mortality with neuromuscular blockade use in ARDS:
        • However, neuromuscular blockade was also not associated with increased harm
      • As such, it can be considered in patients who remain dyssynchronous with the ventilator despite appropriate sedation
• In well-sedated and possibly chemically relaxed patients:
  • The first maneuver is to provide a recruitment maneuver
  • Recalling that derecruitment is a common cause of hypoxemia:
    • Gently recruiting alveoli can improve oxygenation
  • The damage to the lungs is heterogeneous:
    • Some areas are atelectatic, some are fluid-filled, some are already over distended, and some are even normal:
      • The concept behind a recruitment maneuver is simple:
        • The application of sustained pressure to open up collapsed alveoli:
          • However, there are two potential downsides:
            • Note that the normal and overdistended areas may also become even more overdistended:
              • This overdistention from the previously “good” parts of the lung can lead to decreased gas exchange during the recruitment, causing desaturation
                • This effect should be temporary and improve after the maneuver
        • The second effect is that the patient can become hemodynamically unstable:
          • Due to a significant increase in the intrathoracic pressure and resultant decrease in preload and increase in right ventricular afterload:
          • Again, this should be temporary and resolved with a reduction in the pressure, but in unstable or preload dependent patients, this can precipitate hemodynamic collapse
      • Recruitment maneuvers should never be performed without a respiratory therapist, nurse, and physician present:
        • All clinicians should be aware of the risks of transient hypoxemia and hypotension
• There are many methods of performing recruitment maneuvers:
  • One of the methods least likely to cause hemodynamic perturbations is:
    • To serially increase PEEP in small increments
  • The FiO2 should be set at 1.0 and the patient appropriately sedated, and relaxed if needed
  • The ventilator should be set to pressure control ventilation:
    • With a PC of 15 cmH2O
    • Inspiratory time of 3 sec
    • Rate of 10 breaths per minute
  • Then, increase PEEP 3 cmH2O every 5 breaths until the applied PEEP:
    • Is between 25 to 35 cmH2O and the maximum PIP is between 40 to 50 cmH2O
  • Ventilate at this level for 1 min
    • If the patient desaturates or becomes hypotensive at any point, stop, and return to the prior PEEP.
  • From here, the best compliance decremental PEEP trial should be performed
  • The next step is to change to volume control ventilation (VCV) at 4 to 6 ml/kg PBW and set PEEP at 20 to 25 dependent on patient severity of lung injury
  • The respiratory rate should be set to a rate that does not result in autoPEEP, usually 20 to 30 breaths/minute
  • Measure dynamic compliance:
    • Then decrease the PEEP by 2 cmH2O, holding for 30 seconds at a time, and reassessing dynamic compliance each time:
      • Initially the compliance will increase as PEEP is decreased, but with derecruitment, compliance will decrease
  • Once it is obvious that compliance is decreasing, the trial can be stopped
  • A clear pattern will indicate the PEEP with the best compliance
  • To set the ventilator, recruit the lung a second time, then set at the best PEEP + 2cmH2O to optimize oxygenation as well
• For patients with a PaO2/FiO2 ratio of less than 150:
  • The next maneuver is proning the patient, or placing them in the proned position, to improve oxygenation to the posterior lungs
  • Proning the patient improves V/Q matching and allows the patient to have gas exchange along the posterior aspects of the lungs
  • Proning has been shown to improve mortality in severe ARDS in a large multi-center study
  • Additionally, patients with COVID-19 seem responsive to proning:
    • However, this maneuver requires specialized expertise and a coordinated effort amongst providers to avoid dislodging the endotracheal tube and patient harm
    • If a patient has such severe hypoxemia that non-Intensivists are considering proning, expert consultation should be sought
• Another consideration is the administration of inhaled pulmonary vasodilators:
  • Such as:
    • Inhaled nitric oxide (not to be confused with nitrous oxide, the anesthetic agent) or
    • Prostacyclins, such as epoprostenol
• Hypoxemic patients generally have heterogeneous lung pathology, with some damaged areas not participating in oxygenation and ventilation, as well as some relatively unharmed areas that are doing the bulk of gas exchange:
  • Inhaled pulmonary vasodilators will vasodilate the areas that are participating in gas exchange, effectively increasing blood flow to the good areas of the lung and allowing the ineffective areas to continue to have hypoxemic vasoconstriction.
• Finally, patients with severe, refractory hypoxemia may be referred to an extracorporeal membrane oxygenation (ECMO) center for consideration of ECMO support:
  • The data for venovenous (VV) ECMO in severe ARDS not related to COVID-19 are mixed:
    • The largest trial, the EOLIA trial,14 ECMO for severe ARDS was stopped early at 249/331 patients enrolled for predefined futility
    • There was no significant mortality benefit at day 60, but 28% of the conventional treatment group had crossover to ECMO rescue
    • This has led to a lot of controversy as to how the results of the trial should be interpreted
    • Although it is a negative trial, proponents of ECMO note that when patients from the control group received ECMO, it was started later when they were sicker, and 7 crossover control patients even underwent VA ECMO for arrest
    • They also note that conventional treatment had a high rate of failure necessitating ECMO

#Arrangoiz #Surgeon #Teacher

There are three settings common to every conventional mode of ventilation:

1. FiO2:
   • The amount of oxygen delivered to the patient
2. PEEP:
   • Pressure maintained in the respiratory system at the end of exhalation:
     • Maintaining PEEP:
       • Keeps an open lung and prevents atelectasis
3. Trigger sensitivity:
   • Criteria used to see if the patient is making an effort:
     • Flow-triggered
     • Pressure-triggered

• The three most common modes of ventilation include:
  • Volume assist control
  • Pressure assist control
  • Pressure support
• Assist control modes (pressure or volume) are:
  • Typically used in the acute phase of mechanical ventilation, or
  • When the patient has no or very minimal drive to breath
• Pressure support:
  • Is used when patients have an intact respiratory drive

• Volume Assist Control (AC-VC):
  • Requires a frequency of respirations per minute
  • Patients can trigger additional breaths greater than the devised respirations per minute
  • If the trigger criteria is not being met, the machine will trigger all of the breaths
  • When patients are starting to interact with the ventilator:
    • A spontaneous mode:
      • Such as pressure support should be considered
  • The tidal volume should be 6 to 8 mL/kg of ideal body weight:
    • The weight should be predicted weight, NOT actual weight:
      • As actual weight will overestimate the tidal volume
    • To calculate predicted weight we relied on the work of emDocs, and the group recommends using the equation:
      • 50 + 2.3 x (height [in] – 60) for men
      • 45 + 2.3 x (height [in] – 60) for women
  • Current practice based on several trials suggests:
    • That the patient should be ventilated with “lower” tidal volumes of 6 to 8 mL/kg
  • Flow:
    • Is the speed at which the tidal volume is delivered:
      • 50 to 60 L / min will minimize discomfort when patients start making an effort
  • PEEP should always be set at a minimum of:
    • 5 cmH2O:
      • To reduce atelectasis
  • The inspiratory flow:
    • Is commonly set between 50 and 60 L/min and
    • A minimum I:E ratio of:
      • 1:1.5 to 1:2:
        • Affected by respiratory rate as well
    • Common inspiratory times are:
      • 0.75s to 1 s
    • In certain circumstances:
      • Such as in airway obstruction with asthma:
        • Allowing more time for exhalation is beneficial:
          • In these cases:
            • One can increase the inspiratory flow or
            • Decrease the I:E ratio:
              • To 1:3 or 1:4
  • The inspiratory pause:
    • Helps distinguish between:
      • Resistive pressure and elastic pressure (compliance of the respiratory system)
    • Allows the ventilator to display the:
      • Plateau pressure:
        • Which is helpful for monitoring the patient’s respiratory system mechanics (resistance and compliance)
    • It also prolongs the inspiratory time to the common time of 0.75s to 1 s

• Pressure Assist Control (AC-PC):
  • Similarly requires a frequency of respirations per minute
  • The inspiratory time:
    • Is the length of time the pressure is maintained
  • The rise time:
    • Is the time the ventilator will take to reach the set pressure:
      • The default setting for rise time is generally acceptable at:
        • 0.1 sec
  • As resistance or elastance of the respiratory system changes:
    • A result will be changes in:
      • Tidal volume and minute ventilation
        • Consequently, it is very important to monitor the tidal volume and keep it in the proper range in AC-PC
  • The I:E ratio:
    • Is the simplest parameter to monitor if there is enough time to exhale:
      • It must be maintained at 1:2 or higher to ensure there is enough time to exhale
        • If the patient starts spontaneously breathing, this will affect I:E and it is worth considering transition to spontaneous breathing
  • Similar to volume assist control:
    • The inspiratory flow is commonly set at:
      • 60 L/min
    • Tidal volume should be:
      • 6 to 8 mL/kg

• Pressure Support (PS):
  • Is distinguished from AC-PC:
    • Because breaths are cycled off by a % of peak flow:
      • As opposed to time
  • It is important to adjust the default settings for the % of peak flow to initiate the cycling off of each breath:
    • As it depends highly on the resistance and elastance of the lungs

Levels to monitor:

• Volume Assist Control:
  • Elevated peak pressure and/or plateau pressure:
    • Will result from abnormal resistance and elastance due to:
      • ARDS, COPD, asthma, intra-abdominal hypertension, etc.
• Pressure Assist Control:
  • Significant changes to tidal volume and minute ventilation:
    • Will result from abnormal resistance and elastance due to:
      • ARDS, COPD, asthma, intra-abdominal hypertension, etc.
• PEEP:
  • Can be increased to improve oxygenation:
    • However, it should not be so much to overdistend the lungs
    • The risk of potential injury increases:
      • When plateau pressure is greater than:
        • 27 cm H2O

• pH should be kept between 7.35 and 7.45:
  • To increase pH:
    • Increase minute ventilation
  • To decrease pH:
    • Decrease minute ventilation
  • However:
    • Minute Ventilation should not be increased to the point that PaCO2 < 30 mmHg:
      • Cerebral perfusion may be impacted with levels that low
  • In management of ARDS:
    • Permissive hypercapnia is often considered to minimize injury to the lung and a pH 7.25 is considered the lower acceptable limit

#Arrangoiz #Surgeon #Teacher

• Just as important as knowing when and how to put a patient on a ventilator:
  • It is important to know when and how to remove them from this support:
    • Also known as “weaning
• An adage from Critical Care is that preparation for extubation:
  • Starts as soon as the patient is intubated
• With COVID-19:
  • The patients are generally requiring prolonged periods of intubation:
    • With many reports quoting 10 to 14 days
• Regardless, the onus falls on the clinicians caring for any mechanically ventilated patient to assess the patient’s daily for signs of stability or improvement:
  • With any signs of improvement, assessment for extubation readiness should begin
• Patients’ conditions should be assessed continually:
  • And once gas exchange and compliance improve:
    • The level of support can be reduced
• For most patients, the first step in moving towards extubation readiness is:
  • To move from assist control ventilation to pressure support ventilation:
    • Pressure support ventilation:
      • Allows for spontaneous ventilation
        • The patient engages their diaphragm and sets their own respiratory rate, flow, and tidal volume
• The following ventilator screen illustrates a patient who is ready to be changed to pressure support:
  • The patient was arousable with:
    • Lightening sedationhas
    • Has good pulmonary mechanics as indicated by:
      • The low PIP of only 22 with a TV of 400, has a low PEEP requirement, and is only on 50% FiO2
  • On these settings, the patient’s ABG was also reassuring, at 7.37/38/110:
    • Note:
      • In addition to changing to pressure support, the FiO2 could also be decreased to 40% given the more than adequate PaO

• Once the patient has been placed on pressure support:
  • Physiological measurements including:
    • MIP (maximal inspiratory pressure),
    • frVt (respiratory frequency to tidal volume ratio, or
    • Rapid shallow breathing index
      • and others can be used to assess a patient’s readiness to wean
• If the following criteria are met:
  • The patient should undergo a spontaneous breathing trial (SBT) to determine if they are ready to attempt extubation

• Criteria for Performing Spontaneous Breathing Trial:
  • Improvement of underlying condition that led to intubation
  • Relative hemodynamic stability
    • HR < 130 beast per minute
    • Mean arterial pressure (MAP):
      • Adequately supported on a stable dose of vasopressors
    • Presence of a cough reflex:
      • Often elicited by suctioning
    • Burden of secretions that can be handled by cough strength:
      • Patients with a robust cough will be able to clear more secretions
    • Adequate oxygenation:
      • Usually SpO2 > 90% on 40% FiO2 and PEEP ≤ 8
    • Ability to maintain the current oxygenation status once extubated
    • Adequate ventilation:
      • pH > 7.3 with a PCO2 near baseline
      • Minute ventilation that a patient can maintain after extubated:
        • Usually < 12 L/min
    • Minimal ventilator settings:
      • On pressure support ≤ 10 cmH2O
      • On PEEP ≤ 8 cmH2O
      • Maintaining tidal volumes ≥ 5 mL/kg PBW
      • Respiratory rate < 35
      • FiO2 ≤ 50%

• The following screen shows a patient on pressure support, 10/5 (10 cm H20 driving pressure over 5 cm H2O of PEEP):
  • This patient is marginal, as the tidal volume with 10 cm H2O of driving pressure is 400, which is acceptable, but the respiratory rate is 30:
    • The patient should be assessed for non-pulmonary causes of tachypnea:
      • Such as pain, anxiety/agitation, fever, etc
    • It is reasonable to decrease the pressure support of 10 cm H2O and reassess both the tidal volumes and respiratory rate
    • It is difficult to predict how patients will do; often the best course is to give them a trial and assess

• Spontaneous breathing trials are used to:
  • Assess a patient’s readiness to wean by removing ventilation support for 30 minutes and evaluating the patient’s ability to breathe on their own during this time
  • There are many ways to perform SBTs, including:
    • Pressure support of 5/5, 0/5, and 0/0, as well as “T-piece trials” in which the patient is taken off the ventilator and supported with blow-by humidified oxygen
    • Each approach has its proponents, and institutional guidelines vary
      • The most important concept to consider is the available respiratory support options once the patient is intubated, and ensure they are able to pass with that level of support

• Criteria for Passing Spontaneous Breathing Trials:
  • Clinical Appearance:
    • No evidence of respiratory distress:
      • Cyanosis
      • Diaphoresis
      • Accessory muscle use
      • Grimacing
  • Pulmonary mechanics
    • Ratio of respiratory rate : tidal volume:
      • Less than 105
    • Respiratory rate less than 30 breaths per minute
    • Tidal volume less than 5 mL/kg PBW
  • Oxygenation and ventilation:
    • SpO2 ≤ 50%
    • PaC02 ≤ 50mmHg or a
    • pH ≥ 7.3 or decrease in pH of ≤ 0.07
  • Hemodynamics:
    • Change in SBP to > 90 or < 180 mmHg
    • HR < 130 beats per minute
    • New dysrhythmias
• The screen below demonstrates a patient who is doing well on an SBT:
  • They are on pressure support, 5/5, and have large tidal volumes of 735 mL, indicating good compliance
  • They are breathing at a slow rate of 14, and they are on a low FiO2 of 25%
  • This patient would be an excellent candidate for extubation, assuming there are no other barriers

• If a patient’s spontaneous breathing trial is successful, the next step is to assess for other barriers to extubation
• A helpful approach is to go head to toe:
  • Head:
    • Is the patient awake, following commands?
      • If not, does the clinician believe s/he will be able to cough and protect the airway?
    • Is the patient calm or agitated?
      • If agitated, does it seem related to the ETT?
      • Is there a plan for agitation management?
    • Is pain adequately controlled without inducing somnolence or apnea?
• Face/Neck:
  • Any facial trauma?
    • Tongue or lip swelling?
      • Note:
        • This may be seen in a patient who was previously proned
  • Was the patient a difficult intubation?
    • Note:
      • Does not preclude extubation, but all clinicians should be aware
  • Does the patient have a cuff leak?
• Chest:
  • Does the patient have any chest trauma/other pathology (eg, rib fractures, etc) that may preclude adequate breathing?
• Abdomen:
  • Any planned procedures or diagnostics that should happen before extubation?
  • What is the nutrition plan after extubation?
  • Should an NG tube be placed for tube feeds before extubation?
    • Note:
      • Most patients with prolonged intubations have oropharyngeal muscle weakness for days after extubation, precluding normal feeding
• If there are no barriers to extubation, the patient may be extubated:
  • In preparation, gather supplies that would be needed for oxygenation post-extubation (nasal cannula, oxygen mask, CPAP or BPAP, etc.), as well as supplies that would be needed to intubate the patient again if extubation fails:
    • Endotrachial tubes (ETTs) of appropriate sizes
    • Bag mask with positive end expiratory-pressure (PEEP) valve
    • Airway bougies
    • Tube exchangers
    • Traditional direct laryngoscope
    • Video laryngoscope
    • Flexible bronchoscope
    • Drugs needed for induction
    • Suction catheter
• For extubation:
  • Put the patient in an upright, seated position
  • Suction the ETT and oral cavity
  • Remove all secretions above the ETT cuff using subglottic suction, if available, or insert a small bore catheter on the side of the ETT for removal of secretions above the ETT cuff
  • Remove the ETT from the holder
  • Ask the patient to take a deep breath and exhale
  • During exhalation, deflate the cuff and smoothly remove the ETT
    • Note:
      • If an orogastric tube is present, it will be removed alongside the ETT and may need to be replaced by a nasogastric tube, if the patient is not ready for oral intake of medications and nutrition
  • Suction the oral cavity
  • Ask the patient to take a deep breath and cough out all secretions
  • Provide supplemental oxygen through a nasal cannula, oxygen mask, etc., as appropriate
  • After extubation, it is important to monitor the patient carefully:
    • Make sure they have adequate oxygenation and provide supplemental oxygen as appropriate
    • If necessary, consider CPAP/BPAP if a patient requires additional support
    • Use bronchodilators as needed, provide secretion management, maintain airway hydration and patent central airway, and encourage patient behaviors that reduce the potential for re-intubation:
      • Coughing
      • Deep breathing
      • Sitting up
      • Moving around if appropriate
• Risk factors that suggest a patient will need to be re-intubated include:
  • Pneumonia
  • Weak cough
  • Frequent suctioning
  • Rapid shallow breathing index > 58 breaths per minute per liter
  • Positive fluid balance in the 24 hours prior to extubation

Extubation process and post-extubation recommendations modified from Saeed F, Lasrado S. Extubation. [Updated 2019 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539804/

#Arrangoiz #Surgeon #Teacher

Asthma

• In asthma:
  • The patient has a constriction of the bronchial smooth muscles in the airways:
    • Leading to reversible air trapping:
      • This is indicated in the picture:
        • Note that the bronchial muscles do not extend into the small airways

• Intubation of an asthmatic is a dreaded complication of this illness:
  • As asthmatics can deteriorate rapidly on the ventilator:
    • Without close monitoring and active management
  • The goal with a ventilated asthmatic:
    • Is to prevent breath-stacking or autoPEEP:
      • And the hemodynamic instability that can result

• Clinicians should note that intubation of an asthmatic:
  • Should trigger even more active management with medications, rather than less
• Intubated asthmatic patients should continue to receive aggressive treatment with:
  • Bronchodilators
  • Steroids
  • Magnesium
  • As well as deep sedation:
    • Possibly even neuromuscular blockade in the initial hours after intubation:
      • In an effort to relax the chest wall musculature and gain control of the situation
    • Please note that neuromuscular blockade:
      • Only works on skeletal muscle and therefore:
        • Will not bronchodilate smooth muscle in the airways
• In addition:
  • It is very critical to be aware of the patient’s intravascular volume status:
    • As the excess positive pressure:
      • Can lead to hemodynamic collapse
  • Moreover, the excess pressure, including the auto-PEEP:
    • Can result in barotrauma:
      • Such as the development of a pneumothorax very quickly in this patient population
• The ventilator screen below demonstrates the effects of reactive airways disease on pulmonary mechanics:
  • This patient had unexpected bronchospasm after being intubated:
    • Note the elevated peak inspiratory pressure (PIP) of 45 despite the relatively low tidal volume of 365:
      • The patient’s resistance was too high for her to even receive the full tidal volume, as the ventilator was only able to deliver 320 ml before stopping

• Checking the plateau pressure (Pplat):
  • Confirmed that this was a resistance problem, rather than a pure compliance problem:
    • Her PIP was 39 at the time the inspiratory hold was performed:
      • But her Pplat was only 28:
        • The delta between 39 and 28 indicates a significant resistance component

• This patient was treated with continuous bronchodilators with rapid improvement in the bronchospasm:
  • Her PIP returned to normal within minutes
• Four ventilator maneuvers:
  • Increase expiratory time:
    • Decreasing the respiratory rate
    • Decreasing the I:E ratio
    • Decreasing the inspiratory time
    • Increasing the inspiratory flow
      • Of these, decreasing the respiratory rate is the most effective means:
        • To allow more time to exhale
• The figure shows a picture of 30 seconds with two patients, set with the same I:E ratio of 1:2:
  • The first patient:
    • Has a rate of 10 breaths per minute:
      • Allowing 6 seconds per breath cycle
  • The second patient:
    • Has only 3 seconds per breath cycle:
    • Given the respiratory rate of 20
  • The blue represents inspiration, the red the time for exhalation:
    • Note that even with the same I:E ratio:
      • The lower rate offers a substantially longer time to exhale

• In looking further at this diagram:
  • One can imagine the effects of changing the I:E ratio, the inspiratory flow, or the I time:
    • The following figure shows a hypothetical example of the effects of these changes in a patient on volume control:
      • In a given patient, the exact values will vary, but the purpose of the illustration is to show the relationship among the parameters of:
        • I:E ratio, inspiratory time, and inspiratory flow

• In addition to a slow respiratory rate, a low I:E ratio, a short inspiratory time and/or a fast inspiratory flow rate:
  • Asthmatics should also be ventilated with:
    • Low tidal volumes:
      • Considering that the larger the tidal volume:
        • The more the patient has to exhale
• In monitoring an intubated asthmatic, looking for air trapping is key:
  • In the ventilator tracing below, note that the flow tracing, in the middle, does not return to the baseline before the next breath. (Red arrows):
    • This represents that the patient is still exhaling when the next breath is given:
      • Leading to air trapping:
        • Seeing this pattern on the ventilator can be an early clue that the patient is air trapping

• In this patient:
  • You could first decrease the respiratory rate, or increase sedation if the patient is over-breathing
  • The I:E ratio is only 1:2:
    • So changing the I time to make a ratio of 1:3 or 1:4 is also appropriate
  • Also continued treatment with bronchodilators:
    • To decrease the bronchospasm associated with this disease:
      • Will also mitigate the excess auto-PEEP
• Recall that to quantify the pressure exerted by air trapping:
  • One should check for autoPEEP:
  • B y checking an expiratory hold button on the mechanical ventilator

• The intrinsic PEEP is 11, and the total PEEP is 12:
  • This indicates that the patient was only set on 1 of PEEP (an unusual – and not recommended – setting, used in this circumstance for demonstration purposes only.)
• Thus, to set the ventilator for an asthmatic, select:
  • A low tidal volume:
    • 6 to 8 mL/kg of predicted body weight
  • The respiratory rate should be low:
    • Less than 20 breaths per minute:
      • Oten around 10 breaths per minute
  • The I:E ratio should be changed to:
    • 1:3 or less
  • PEEP should be set at:
    • 5 cmH2O
  • The FiO2 should be down-titrated as tolerated
  • These patients continue to receive:
    • Heavy sedation
      • Possibly NMB if required
    • Continuous bronchodilators
    • Close monitoring for breath stacking and autoPEEP:
      • AutoPEEP should be monitored periodically or after any ventilator change:
        • With an expiratory hold
    • Arterial blood gases (ABGs) should be checked:
      • To ensure that the patient is being adequately ventilated
• Permissive hypercapnia:
  • Is the concept of tolerating a PaCO2 greater than 40mmHg and a pH greater than 7.20 to 7.25:
    • For the sake of achieving another goal:
      • In the case of asthma:
        • The goal is to allow time to exhale and prevent air-trapping:
          • Permissive hypercapnia is a reasonable strategy:
            • Especially early in ventilating the asthmatic
• Initial Ventilator Settings in Asthma:
  • Tidal Volume:
    • 6 to 8 ml/kg PBW
  • Respiratory Rate:
    • 6 to 14 breaths/minute:
      • Allowing for permissive hypercapnia
  • PEEP:
    • ~ 5 cmH2O
  • FiO2:
    • Decrease as tolerated
  • SpO2 ≥ 92%
• The following ventilator screen demonstrates these settings:
  • The patient is set at 6ml/kg at 350 mls, with a respiratory rate of 14, a PEEP of 5, and a FiO2 40%:
    • Note, however, that the patient is not synchronous with the ventilator and is taking large tidal volumes:
      • This can be a very dangerous situation, leading to worsening air-trapping and possibly hemodynamic compromise:
        • This patient needs to be deeply sedated and neuromuscular blockade administered if needed:
      • Additionally, the patient should continue to receive bronchodilators and all other appropriate medical treatments

COPD

• There are two types of obstructive lung disease falling under the umbrella of COPD:
  • Namely:
    • Chronic bronchitis
    • Emphysema
  • While some patients may have one or the other:
    • Many will exist on the continuum

• Chronic bronchitis can resemble the asthmatic schematic above:
  • With the notable exception that:
    • Muscles hypertrophy and are not entirely reversible
  • Additionally, chronic bronchitis is associated with:
    • Increased mucous production

• Emphysema:
  • Is a disease of parenchymal destruction:
    • Not only is there loss of alveoli:
      • Resulting in decreased surface area, or decreased diffusion area (leading to an increased DLCO):
        • But the small airways:
          • Can become floppy:
            • Due to the loss of other tissues holding them open

• Understanding the pathophysiology of COPD is important for considering how to best ventilate these patients:
  • It should be noted, however:
    • That most patients with COPD have:
      • Some mixing of elements of chronic bronchitis and emphysema:
        • These conditions exist on a spectrum rather than a dichotomy
• Most patients with COPD are now managed:
  • With BPAP:
    • With improved outcomes over intubation:
      • However, on occasion:
        • A patient with COPD is not a candidate for BPAP or fails to improve with a trial of BPAP:
          • Mandating intubation and invasive mechanical ventilation
  • Many of the principles that apply in mechanical ventilation for asthma also apply in COPD:
    • Both are obstructive diseases, and in both processes:
      • The patients require adequate time to exhale:
        • Therefore:
          • Low tidal volumes
          • Low respiratory rates
          • Low I:E ratios:
            • Are appropriate:
              • However, a key difference involves the role of PEEP
  • Patients with COPD:
    • Are at high risk of developing autoPEEP:
      • Due to their obstructive disease:
        • They require additional time to exhale
    • However, the mechanism of obstruction can differ between asthma and COPD:
      • Especially COPD with emphysematous changes as illustrated above:
        • With the destruction of parenchyma, the small airways can collapse with exhalation:
          • Trapping air behind:
            • In this circumstance, this trapped air leads to autoPEEP
              • Increasing the set PEEP, to match the autoPEEP, is not necessarily an intuitive solution:
                • However, as illustrated by the diagram below, increasing the PEEP to prevent collapse of these small airways:
                  • Can allow the patient to exhale more fully

• Reexamine the tracing of the figure from the Asthma section:
  • Imaging that this patient has COPD:
    • If this patient has 11 of autoPEEP, or intrinsic PEEP, what PEEP would you select?

• To match the autoPEEP:
  • 11 cmH2O would be an appropriate PEEP selection
• Lastly:
  • Patients with COPD are often chronically hypoxemic:
    • Indications of chronic hypoxemia physical exam findings of chronic hypoxemia can be demonstrated with nail clubbing
    • Additionally, can include an elevated hemoglobin level on the CBC:
      • Indicating the patient’s compensation for their chronic lung disease
    • Because these patients are baseline hypoxemic, and ventilation is often a relatively greater issue for them than hypoxemia:
      • The oxygen saturation for a patient with COPD should be targeted at 88% to 92% in most circumstances:
        • This is increasingly important as more data demonstrating the risks of hyperoxia continue to accumulate
• Initial Ventilator Settings in COPD:
  • Tidal Volume:
    • 6 to 8 ml/kg PBW
    • Respiratory Rate
      • 6 – 20 breaths/minute:
        • Allowing for permissive hypercapnia
    • PEEP
      • 5 to 15 cmH2O:
        • May need to match autoPEEP:
          • For patients with significant emphysematous physiology
    • Fi02:
      • Decrease as tolerated
    • SpO2 target:
      • 88% to 92%

• This ventilator screen demonstrates a patient with COPD with severe dyssynchrony:
  • The PIP is 54:
    • Indicating severe pathology
  • The irregular waveforms:
    • Indicate the dyssynchrony
  • The patient is set at a respiratory rate of 16 but is breathing at 24

• An expiratory hold was performed and demonstrated a:
  • Total PEEP of 29, with a set PEEP of 10
    • This indicates a high autoPEEP of 19:
      • Therefore, this is a very high-risk situation:
        • This patient was deeply sedated, NMB administered, and the ETT was disconnected from the ventilator to allow the patient to exhale

• Once sedated and relaxed, the patient was placed back on the ventilator at a rate of 12, with frequent expiratory holds to check the autoPEEP

#Arrangoiz #Surgeon #Teacher #CancerSurgeon #MechanicalVentilation

• Critically ill patients are at high risk of deterioration with intubation and initiation of mechanical ventilation
• Much of this summary is devoted to reviewing the effects of positive pressure ventilation (PPV) can have on pulmonary physiology:
  • However, mechanical ventilation can also have:
    • Extra-pulmonary effects that warrant review:
      • Specifically, PPV leads to:
        • An increase in the intrathoracic pressure:
          • Which has different effects on the right and left ventricles:
            • For the right ventricle, the PPV will lead to decreased preload via decreased venous return
              • This is shown by the blue and white arrowheads indicating increased pressure
            • The distention of the alveoli can also lead to increased afterload on the right ventricle
              • The inset illustrates the compression of small capillaries by distended alveoli:
                • Leading to an increase in pulmonary vascular resistance

• Note, however, that there is a U-shaped curve for changes in the pulmonary vascular resistance:
  • Both atelectasis and overdistention can:
    • Increase the afterload on the right ventricle

• The effects on the left ventricle are slightly different:
  • PPV also decreases the left ventricular preload:
    • Given the impact on the right ventricle
  • However:
    • The increased intrathoracic pressure also decreases the transmural pressure, or:
      • The afterload, on the left ventricle:
        • While we use this principle to care for those with congestive heart failure (CHF):
          • Can lead to an increase in stroke volume and cardiac output

• However, in excess, these impacts on the cardiovascular system can lead:
  • To a decrease in the cardiac output and hypotension:
    • Especially in the intravascularly depleted patient, those with shock physiology, or with air trapping
    • Additionally, PPV leads to a decrease in the left ventricular afterload
• When intubating and placing the patient on the ventilator, the clinician should anticipate these effects:
  • A volume-depleted patient:
    • Such as a patient with a GI bleed, may have hemodynamic collapse with initiation of positive pressure ventilation
• When initiating mechanical ventilation, the practitioner must be conscientious to ensure adequate gas exchange to meet the metabolic demands of the patient:
  • For example, a patient in with metabolic acidosis and respiratory compensation might be very tachypneic:
    • One must be cognizant to increase the respiratory rate on the ventilator to help meet the patient’s metabolic demands:
      • Failure to do so can be detrimental for the patient, and lead to rapid decompensation
• Along the same lines, the practitioner must be careful to set and then adjust the ventilator settings to prevent further decompensation or injury:
  • For example:
    • Excessive volumes on the ventilator can lead to:
      • Volutrauma and impaired gas exchange
    • Excess pressure can lead to:
      • Hemodynamic instability or barotrauma

#Arrangoiz #Surgeon #Cancer #Teacher

• The National Surgical Adjuvant Bowel and Breast Project B-18 was designed to:
  • Determine whether preoperative chemotherapy:
    • Would result in improved survival compared to postoperative chemotherapy
  • Secondary aims included:
    • Evaluation of pCR rates
    • Comparison of breast conservation rates and ipsilateral recurrence rates between the two groups
  • Between 1988 and 1993:
    • 1523 patients with clinical T1 to T3 N0 to N1 operable breast cancer were enrolled in the trial:
      • 763 were randomized to preoperative therapy while 760 were randomized to postoperative therapy
  • At 16 years of follow-up:
    • There was no difference in:
      • Disease-free survival (HR = 0.93, 95% CI, 0.81 to 1.06, p = 0.27) or
      • Overall survival (HR = 0.99, 95% CI, 0.85 to 1.16, p = 0.90):
        • Between the postoperative and preoperative chemotherapy groups
  • In the preoperative group:
    • A pCR was documented in 13% of patients
  • Preoperative chemotherapy patients:
    • Had a significantly increased incidence of having pathologically negative nodes compared to postoperative chemotherapy patients:
      • 58% vs. 42%, respectively:
        • p<0.0001
  • The rate of breast conservation:
    • Was higher among women who received neoadjuvant chemotherapy compared to women who received postoperative chemotherapy:
      • 68% versus 60%, respectively:
        • p = 0.001
    • The significant downstaging:
      • Of tumors > 5cm in the preoperative chemotherapy arm:
        • Primarily drove this breast conservation trend
  • There was a trend toward a higher rate:
    • Of ipsilateral breast tumor recurrence with preoperative vs postoperative chemotherapy:
      • 13% of 506 patients vs
      • 10% of 450 patients, respectively:
        • Although this difference was not statistically significant (p = 0.21)
  • Retrospective series later found:
    • No difference in surgical complications between women who received preoperative or postoperative chemotherapy

REFERENCES

1. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16(8):2672-2685.
2. Boughey JC, Peitinger F, Meric-Bernstam F, et al. Impact of preoperative versus postoperative chemotherapy on the extent and number of surgical procedures in patients treated in randomized clinical trials for breast cancer. Ann Surg. 2006;244(3):464–470.
3. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778-785.

#Arrangoiz #BreastSurgeon #BreastCancer #Teacher #SurgicalOncologist #CancerSurgeon

• In 2013:
  • Recognizing that while breast-conserving therapy had become standard practice in the management of early-stage breast cancer:
    • There were no accepted consensus on optimal negative margin width:
      • The SSO and ASTRO convened a multidisciplinary expert panel to:
        • Review the available evidence regarding margin width and ipsilateral breast tumor recurrence (IBTR)
  • Meta-analysis and secondary data from prospective and retrospective trials led them to conclude that:
    • Positive margins:
      • Defined as:
        • Ink on invasive cancer is associated with:
          • At least a 2-fold increase in IBTR
    • However:
      • Meta-analysis and retrospective data provide evidence that:
        • Negative margins (no ink on tumor):
          • Optimize IBTR and
          • That the routine practice of obtaining wider negative margins than ink on tumor:
            • Is not indicated
    • While younger age is associated with both increased IBTR after breast-conserving therapy as well as increased local relapse on the chest wall after mastectomy, there is no evidence that increased margin width nullifies this increased risk of IBTR in younger patients. Classic LCIS at surgical margin is not an indication for re-excision. The significance of pleomorphic LCIS at the margin is uncertain.

REFERENCES

1. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88:553-564.